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  Subjects -> BIOLOGY (Total: 3036 journals)
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BIOCHEMISTRY (240 journals)                  1 2 | Last

Showing 1 - 200 of 240 Journals sorted alphabetically
AAPS PharmSciTech     Hybrid Journal   (Followers: 7)
Acetic Acid Bacteria     Open Access   (Followers: 2)
ACS Central Science     Open Access   (Followers: 9)
ACS Chemical Biology     Full-text available via subscription   (Followers: 278)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 19)
Acta Biochimica Polonica     Open Access  
Acta Crystallographica Section D : Biological Crystallography     Hybrid Journal   (Followers: 10)
Acta Crystallographica Section F: Structural Biology Communications     Hybrid Journal   (Followers: 9)
Advances and Applications in Bioinformatics and Chemistry     Open Access   (Followers: 10)
Advances in Biological Chemistry     Open Access   (Followers: 8)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 7)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20)
African Journal of Biochemistry Research     Open Access   (Followers: 1)
African Journal of Chemical Education     Open Access   (Followers: 2)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
American Journal of Biochemistry     Open Access   (Followers: 9)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 67)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 15)
American Journal of Polymer Science     Open Access   (Followers: 28)
Amino Acids     Hybrid Journal   (Followers: 8)
Analytical and Bioanalytical Chemistry Research     Open Access  
Analytical Biochemistry     Hybrid Journal   (Followers: 171)
Angiogenesis     Hybrid Journal   (Followers: 3)
Annals of Clinical Biochemistry     Hybrid Journal   (Followers: 8)
Annual Review of Biochemistry     Full-text available via subscription   (Followers: 54)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 12)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 42)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 16)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7)
Archives of Biochemistry and Biophysics     Hybrid Journal   (Followers: 20)
Archives of Insect Biochemistry and Physiology     Hybrid Journal  
Archives Of Physiology And Biochemistry     Hybrid Journal   (Followers: 1)
Asian Journal of Biochemistry     Open Access   (Followers: 1)
Bangladesh Journal of Medical Biochemistry     Open Access   (Followers: 3)
BBA Clinical     Open Access  
BBR : Biochemistry and Biotechnology Reports     Open Access   (Followers: 4)
Biocatalysis     Open Access  
Biochemical and Biophysical Research Communications     Hybrid Journal   (Followers: 23)
Biochemical and Molecular Medicine     Full-text available via subscription   (Followers: 4)
Biochemical Compounds     Open Access  
Biochemical Engineering Journal     Hybrid Journal   (Followers: 15)
Biochemical Genetics     Hybrid Journal   (Followers: 3)
Biochemical Journal     Full-text available via subscription   (Followers: 24)
Biochemical Pharmacology     Hybrid Journal   (Followers: 10)
Biochemical Society Transactions     Full-text available via subscription   (Followers: 4)
Biochemical Systematics and Ecology     Hybrid Journal   (Followers: 3)
Biochemistry     Full-text available via subscription   (Followers: 339)
Biochemistry & Pharmacology : Open Access     Open Access   (Followers: 3)
Biochemistry & Physiology : Open Access     Open Access  
Biochemistry (Moscow)     Hybrid Journal   (Followers: 4)
Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology     Hybrid Journal   (Followers: 3)
Biochemistry (Moscow) Supplemental Series B: Biomedical Chemistry     Hybrid Journal   (Followers: 3)
Biochemistry and Biophysics Reports     Open Access  
Biochemistry and Cell Biology     Hybrid Journal   (Followers: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6)
Biochemistry and Molecular Biology of Fishes     Full-text available via subscription   (Followers: 1)
Biochemistry Research International     Open Access   (Followers: 6)
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids     Hybrid Journal   (Followers: 7)
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease     Hybrid Journal   (Followers: 14)
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research     Hybrid Journal   (Followers: 9)
Biochimie     Hybrid Journal   (Followers: 7)
Biochimie Open     Open Access  
Bioconjugate Chemistry     Full-text available via subscription   (Followers: 30)
BioDrugs     Full-text available via subscription   (Followers: 7)
Bioelectrochemistry     Hybrid Journal   (Followers: 2)
Biofuels     Hybrid Journal   (Followers: 11)
Biogeochemistry     Hybrid Journal   (Followers: 14)
BioInorganic Reaction Mechanisms     Hybrid Journal   (Followers: 1)
Biokemistri     Open Access  
Biological Chemistry     Partially Free   (Followers: 22)
Biomaterials Research     Open Access   (Followers: 4)
Biomedicines     Open Access   (Followers: 1)
BioMolecular Concepts     Hybrid Journal   (Followers: 2)
Bioscience, Biotechnology, and Biochemistry     Hybrid Journal   (Followers: 22)
Biosimilars     Open Access   (Followers: 1)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 44)
Bitácora Digital     Open Access  
BMC Biochemistry     Open Access   (Followers: 14)
Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca : Food Science and Technology     Open Access  
Carbohydrate Polymers     Hybrid Journal   (Followers: 8)
Cell Biochemistry and Biophysics     Hybrid Journal   (Followers: 6)
Cell Biochemistry and Function     Hybrid Journal   (Followers: 7)
Cellular Physiology and Biochemistry     Open Access   (Followers: 3)
ChemBioChem     Hybrid Journal   (Followers: 7)
Chemical and Biological Technologies for Agriculture     Open Access  
Chemical Biology & Drug Design     Hybrid Journal   (Followers: 20)
Chemical Engineering Journal     Hybrid Journal   (Followers: 46)
Chemical Senses     Hybrid Journal   (Followers: 1)
Chemical Speciation and Bioavailability     Open Access   (Followers: 1)
Chemico-Biological Interactions     Hybrid Journal   (Followers: 3)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 7)
Chemistry & Biology     Full-text available via subscription   (Followers: 31)
Chemistry and Ecology     Hybrid Journal  
ChemTexts     Hybrid Journal  
Clinica Chimica Acta     Hybrid Journal   (Followers: 33)
Clinical Biochemist Reviews     Full-text available via subscription   (Followers: 1)
Clinical Biochemistry     Hybrid Journal   (Followers: 18)
Clinical Chemistry     Full-text available via subscription   (Followers: 68)
Clinical Chemistry and Laboratory Medicine     Hybrid Journal   (Followers: 61)
Clinical Lipidology     Full-text available via subscription   (Followers: 1)
Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology     Hybrid Journal   (Followers: 5)
Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 1)
Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology     Hybrid Journal   (Followers: 6)
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics     Hybrid Journal   (Followers: 2)
Comprehensive Biochemistry     Full-text available via subscription   (Followers: 1)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 11)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 5)
Current Biochemical Engineering     Hybrid Journal  
Current Chemical Biology     Hybrid Journal   (Followers: 2)
Current Medicinal Chemistry     Hybrid Journal   (Followers: 15)
Current Opinion in Chemical Biology     Hybrid Journal   (Followers: 29)
Current Opinion in Lipidology     Hybrid Journal   (Followers: 6)
DNA Barcodes     Open Access  
Doklady Biochemistry and Biophysics     Hybrid Journal   (Followers: 1)
Doklady Chemistry     Hybrid Journal  
Egyptian Journal of Biochemistry and Molecular Biology     Full-text available via subscription  
FABICIB     Open Access  
FEBS Letters     Hybrid Journal   (Followers: 57)
FEBS Open Bio     Open Access   (Followers: 3)
Fish Physiology and Biochemistry     Hybrid Journal   (Followers: 3)
Food & Function     Full-text available via subscription   (Followers: 6)
Foundations of Modern Biochemistry     Full-text available via subscription  
Free Radicals and Antioxidants     Full-text available via subscription   (Followers: 4)
Frontiers in Molecular Biosciences     Open Access   (Followers: 2)
Frontiers in Natural Product Chemistry     Hybrid Journal  
Global Biogeochemical Cycles     Full-text available via subscription   (Followers: 16)
Green Chemistry     Full-text available via subscription   (Followers: 10)
Histochemistry and Cell Biology     Hybrid Journal   (Followers: 5)
Indian Journal of Biochemistry and Biophysics (IJBB)     Open Access   (Followers: 3)
Indian Journal of Clinical Biochemistry     Hybrid Journal   (Followers: 1)
Indonesian Biomedical Journal     Open Access  
Insect Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 3)
International Journal of Biochemistry & Cell Biology     Hybrid Journal   (Followers: 7)
International Journal of Biochemistry and Biophysics     Open Access   (Followers: 1)
International Journal of Biological Chemistry     Open Access   (Followers: 4)
International Journal of Biomedical Nanoscience and Nanotechnology     Hybrid Journal   (Followers: 6)
International Journal of Food Contamination     Open Access  
International Journal of Plant Physiology and Biochemistry     Open Access  
International Journal of Plant Research     Open Access   (Followers: 3)
International Journal of Secondary Metabolite     Open Access   (Followers: 1)
Invertebrate Immunity     Open Access   (Followers: 1)
JBIC Journal of Biological Inorganic Chemistry     Hybrid Journal   (Followers: 4)
Journal of Microbial & Biochemical Technology     Open Access   (Followers: 2)
Journal of Applied Biology & Biotechnology     Open Access   (Followers: 2)
Journal of Bioactive and Compatible Polymers     Hybrid Journal   (Followers: 3)
Journal of Biochemical and Biophysical Methods     Hybrid Journal   (Followers: 4)
Journal of Biochemistry     Hybrid Journal   (Followers: 42)
Journal of Biochemistry and Molecular Biology Research     Open Access  
Journal of Biological Chemistry     Full-text available via subscription   (Followers: 210)
Journal of Biomaterials Science, Polymer Edition     Hybrid Journal   (Followers: 9)
Journal of Carbohydrate Chemistry     Hybrid Journal   (Followers: 7)
Journal of Cellular Biochemistry     Hybrid Journal   (Followers: 5)
Journal of Chemical Biology     Hybrid Journal   (Followers: 3)
Journal of Chemical Neuroanatomy     Hybrid Journal  
Journal of Clinical Lipidology     Hybrid Journal   (Followers: 2)
Journal of Comparative Physiology B : Biochemical, Systemic, and Environmental Physiology     Hybrid Journal   (Followers: 5)
Journal of Drug Discovery and Therapeutics     Open Access  
Journal of Enzyme Inhibition and Medicinal Chemistry     Open Access   (Followers: 3)
Journal of Evolutionary Biochemistry and Physiology     Hybrid Journal   (Followers: 1)
Journal of Food and Drug Analysis     Open Access  
Journal of Forensic Toxicology and Pharmacology     Hybrid Journal   (Followers: 5)
Journal of Inborn Errors of Metabolism and Screening     Open Access  
Journal of Inorganic Biochemistry     Hybrid Journal   (Followers: 7)
Journal of Medical and Biomedical Sciences     Open Access  
Journal of Medical Biochemistry     Open Access   (Followers: 4)
Journal of Medicine and Biomedical Research     Open Access   (Followers: 1)
Journal of Molecular Biochemistry     Open Access   (Followers: 3)
Journal of Molecular Diagnostics     Hybrid Journal   (Followers: 6)
Journal of Neurochemistry     Hybrid Journal   (Followers: 4)
Journal of Nutritional Biochemistry     Hybrid Journal   (Followers: 7)
Journal of Pediatric Biochemistry     Hybrid Journal   (Followers: 1)
Journal of Peptide Science     Hybrid Journal   (Followers: 22)
Journal of Photochemistry and Photobiology B: Biology     Hybrid Journal   (Followers: 3)
Journal of Physiobiochemical Metabolism     Hybrid Journal   (Followers: 1)
Journal of Physiology and Biochemistry     Hybrid Journal   (Followers: 3)
Journal of Plant Biochemistry and Biotechnology     Hybrid Journal   (Followers: 6)
Journal of Steroid Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 2)
Journal of Virology & Antiviral Research     Hybrid Journal   (Followers: 6)
Journal of Wood Chemistry and Technology     Hybrid Journal   (Followers: 10)
La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine     Hybrid Journal  
Lab on a Chip     Full-text available via subscription   (Followers: 38)
Laboratory Techniques in Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 4)
Marine Chemistry     Hybrid Journal   (Followers: 8)
Methods in Enzymology     Full-text available via subscription   (Followers: 11)
Molecular and Biochemical Parasitology     Hybrid Journal   (Followers: 2)
Molecular and Cellular Biochemistry     Hybrid Journal   (Followers: 6)
Molecular Aspects of Medicine     Hybrid Journal   (Followers: 3)
Molecular Informatics     Hybrid Journal   (Followers: 5)
Molecular inhibitors in targeted therapy     Open Access  
Moscow University Chemistry Bulletin     Hybrid Journal   (Followers: 1)
Mycologia     Hybrid Journal  
Mycology : An International Journal on Fungal Biology     Hybrid Journal   (Followers: 5)
Natural Products and Bioprospecting     Open Access   (Followers: 2)
Nature Chemical Biology     Full-text available via subscription   (Followers: 75)
Nature Communications     Open Access   (Followers: 216)
Neurosignals     Open Access  
New Comprehensive Biochemistry     Full-text available via subscription  
NOVA     Open Access  
Novelty in Biomedicine     Open Access  

        1 2 | Last

Journal Cover Archives of Biochemistry and Biophysics
  [SJR: 1.478]   [H-I: 138]   [20 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0003-9861 - ISSN (Online) 1096-0384
   Published by Elsevier Homepage  [3123 journals]
  • The histidine phosphocarrier protein, HPr, binds to the highly
           thermostable regulator of sigma D protein, Rsd, and its isolated helical
           fragments
    • Authors: José L. Neira; Felipe Hornos; Concetta Cozza; Ana Cámara-Artigas; Olga Abián; Adrián Velázquez-Campoy
      Pages: 26 - 37
      Abstract: Publication date: 1 February 2018
      Source:Archives of Biochemistry and Biophysics, Volume 639
      Author(s): José L. Neira, Felipe Hornos, Concetta Cozza, Ana Cámara-Artigas, Olga Abián, Adrián Velázquez-Campoy
      The phosphotransferase system (PTS) controls the preferential use of sugars in bacteria and it is also involved in other processes, such as chemotaxis. It is formed by a protein cascade in which the first two proteins are general (namely, EI and HPr) and the others are sugar-specific permeases. The Rsd protein binds specifically to the RNA polymerase (RNAP) σ70 factor. We first characterized the conformational stability of Escherichia coli Rsd. And second, we delineated the binding regions of Streptomyces coelicolor, HPrsc, and E. coli Rsd, by using fragments derived from each protein. To that end, we used several biophysical probes, namely, fluorescence, CD, NMR, ITC and BLI. Rsd had a free energy of unfolding of 15 kcal mol−1 at 25 °C, and a thermal denaturation midpoint of 103 °C at pH 6.5. The affinity between Rsd and HPrsc was 2 μM. Interestingly enough, the isolated helical-peptides, comprising the third (RsdH3) and fourth (RsdH4) Rsd helices, also interacted with HPrsc in a specific manner, and with affinities similar to that of the whole Rsd. Moreover, the isolated peptide of HPrsc, HPr9−30, comprising the active site, His15, also was bound to intact Rsd with similar affinity. Therefore, binding between Rsd and HPrsc was modulated by the two helices H3 and H4 of Rsd, and the regions around the active site of HPrsc. This implies that specific fragments of Rsd and HPrsc can be used to interfere with other protein-protein interactions (PPIs) of each other protein.
      Graphical abstract image

      PubDate: 2018-01-04T02:09:13Z
      DOI: 10.1016/j.abb.2017.12.017
      Issue No: Vol. 639 (2018)
       
  • MiR-186-5p upregulation inhibits proliferation, metastasis and
           epithelial-to-mesenchymal transition of colorectal cancer cell by
           targeting ZEB1
    • Authors: Jinlei Li; Limin Xia; Zhenhua Zhou; Zhigui Zuo; Chang Xu; Huayu Song; Jianhui Cai
      Abstract: Publication date: Available online 8 January 2018
      Source:Archives of Biochemistry and Biophysics
      Author(s): Jinlei Li, Limin Xia, Zhenhua Zhou, Zhigui Zuo, Chang Xu, Huayu Song, Jianhui Cai
      MicroRNA-186-5p (miR-186-5p) is upregulated and exhibits as a crucial oncogene in various human tumors. However, the functions and underlying mechanisms of this microRNA on colorectal cancer remain largely unknown. Here, we report that miR-186-5p share a lower expression in colorectal cancer cell lines (HT116, H29, SW620 and LoVo) than in normal colonic epithelial cell line NCM460. MiR-186-5p overexpression inhibits proliferation, metastasis and epithelial-to-mesenchymal transition (EMT) of colorectal cancer cell line LoVo. Zinc Finger E-Box Binding Homeobox 1 (ZEB1), an EMT related marker, is predicted as a target of miR-186-5p. Luciferase reporter assay, qRT-PCR and western blot analysis showed that miR-186-5p directly targeted the 3′-untranslated regions (3′UTR) of ZEB1 messenger RNA. Further functional experiments indicated that overexpression of miR-186-5p suppress the proliferation and metastasis ability of LoVo, which was consistent with the inhibitory effects by knockdown of ZEB1. Additionally, overexpression of ZEB1 could significantly reverse the miR-186-5p mimics initiated suppression impact of proliferation, metastasis and EMT on LoVo. In summary, miRNA-186-5p affects the proliferation, metastasis and EMT process of colorectal cancer cell by inhibition of ZEB1. Hence, it may serve as a promising therapeutic target for colorectal cancer.

      PubDate: 2018-01-10T02:48:27Z
      DOI: 10.1016/j.abb.2018.01.002
       
  • Functions and dysfunctions of Ca2+/calmodulin-dependent protein kinase
           phosphatase (CaMKP/PPM1F) and CaMKP-N/PPM1E
    • Authors: Atsuhiko Ishida; Noriyuki Sueyoshi; Isamu Kameshita
      Abstract: Publication date: Available online 6 January 2018
      Source:Archives of Biochemistry and Biophysics
      Author(s): Atsuhiko Ishida, Noriyuki Sueyoshi, Isamu Kameshita
      Intracellular signal transduction is built on the basis of the subtle balance between phosphorylation and dephosphorylation. Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F/POPX2) and CaMKP-N (PPM1E/POPX1) are Ser/Thr phosphatases that belong to the PPM (protein phosphatase, Mg2+/Mn2+-dependent) family. The former was discovered in rat brain as a novel protein phosphatase regulating Ca2+/calmodulin-dependent protein kinases (CaMKs), whereas the latter was first identified in human cDNA databases using the rat CaMKP sequence. Subsequent studies have revealed that they are involved in various cellular functions through regulation of not only CaMKs but also other protein kinases such as AMP-activated protein kinase. Furthermore, accumulating evidence shows possible involvement of CaMKP and CaMKP-N in the pathogenesis of various diseases including cancer. Therefore, the biochemistry of CaMKP and CaMKP-N largely contributes to molecular medicine targeting these phosphatases. In this review, we summarized recent progress in the enzymology and biology of CaMKP and CaMKP-N. We also focused on etiology studies in which CaMKP and CaMKP-N are involved. Based on the emerging evidence, future perspectives of studies on these phosphatases and related issues to be elucidated are discussed.

      PubDate: 2018-01-10T02:48:27Z
      DOI: 10.1016/j.abb.2018.01.001
       
  • Prolonged exposure to 1,25(OH)2D3 and high ionized calcium induces FGF-23
           production in intestinal epithelium-like Caco-2 monolayer: A local
           negative feedback for preventing excessive calcium transport
    • Authors: Mayuree Rodrat; Kannikar Wongdee; Natthaphon Panupintu; Jirawan Thongbunchoo; Jarinthorn Teerapornpuntakit; Nateetip Krishnamra; Narattaphol Charoenphandhu
      Abstract: Publication date: Available online 6 January 2018
      Source:Archives of Biochemistry and Biophysics
      Author(s): Mayuree Rodrat, Kannikar Wongdee, Natthaphon Panupintu, Jirawan Thongbunchoo, Jarinthorn Teerapornpuntakit, Nateetip Krishnamra, Narattaphol Charoenphandhu
      Overdose of oral calcium supplement and excessive intestinal calcium absorption can contribute pathophysiological conditions, e.g., nephrolithiasis, vascular calcification, dementia, and cardiovascular accident. Since our previous investigation has indicated that fibroblast growth factor (FGF)-23 could abolish the 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-enhanced calcium absorption, we further hypothesized that FGF-23 produced locally in the enterocytes might be part of a local negative feedback loop to regulate calcium absorption. Herein, 1,25(OH)2D3 was found to enhance the transcellular calcium transport across the epithelium-like Caco-2 monolayer, and this stimulatory effect was diminished by preceding prolonged exposure to high-dose 1,25(OH)2D3 or high concentration of apical ionized calcium. Pretreatment with a neutralizing antibody for FGF-23 prevented this negative feedback regulation of calcium hyperabsorption induced by 1,25(OH)2D3. FGF-23 exposure completely abolished the 1,25(OH)2D3-enhanced calcium transport. Western blot analysis revealed that FGF-23 expression was upregulated in a dose-dependent manner by 1,25(OH)2D3 or apical calcium exposure. Finally, calcium-sensing receptor (CaSR) inhibitors were found to prevent the apical calcium-induced suppression of calcium transport. In conclusion, prolonged exposure to high apical calcium and calcium hyperabsorption were sensed by CaSR, which, in turn, increased FGF-23 expression to suppress calcium transport. This local negative feedback loop can help prevent unnecessary calcium uptake and its detrimental consequences.

      PubDate: 2018-01-10T02:48:27Z
      DOI: 10.1016/j.abb.2017.12.022
       
  • Structure, kinetics, molecular and redox properties of a cytosolic and
           developmentally regulated fungal catalase-peroxidase
    • Authors: Vanessa Vega-García; Adelaida Díaz-Vilchis; Juan-Pablo Saucedo-Vázquez; Alejandro Solano-Peralta; Enrique Rudiño-Piñera; Wilhelm Hansberg
      Abstract: Publication date: Available online 2 January 2018
      Source:Archives of Biochemistry and Biophysics
      Author(s): Vanessa Vega-García, Adelaida Díaz-Vilchis, Juan-Pablo Saucedo-Vázquez, Alejandro Solano-Peralta, Enrique Rudiño-Piñera, Wilhelm Hansberg
      CAT-2, a cytosolic catalase-peroxidase (CP) from Neurospora crassa, which is induced during asexual spore formation, was heterologously expressed and characterized. CAT-2 had the Met-Tyr-Trp adduct required for catalase activity. Its K M for H2O2 was micromolar for peroxidase and millimolar for catalase activity. A Em = −158 mV reduction potential value was obtained and the Soret band shift suggested a mixture of low and high spin ferric iron. CAT-2 EPR spectrum at 10 K indicated an axial and a rhombic component. With peroxyacetic acid (PAA), formation of Compound I* was observed with EPR. CAT-2 homodimer crystallographic structure contained two K+ ions; Glu107 residues were displaced to bind them. CAT-2 showed the essential amino acid residues for activity in similar positions to other CPs. CAT-2 Arg426 is oriented towards the M-Y-W adduct, interacting with the deprotonated Tyr238 hydroxyl group. A perhydroxy modification of the indole nitrogen of Trp90 was oriented toward the catalytic His91. In contrast to cytochrome c peroxidase and ascorbate peroxidase, the catalase-peroxidase heme propionates are not exposed to the solvent. Together with other N. crassa enzymes that utilize H2O2 as a substrate, CAT-2 has many tryptophan and proline residues at its surface, probably related to H2O2 selection in water.
      Graphical abstract image

      PubDate: 2018-01-04T02:09:13Z
      DOI: 10.1016/j.abb.2017.12.021
       
  • Progress curve analysis of the kinetics of slow-binding anticancer drug
           inhibitors of the 20S proteasome
    • Authors: Brian B. Hasinoff
      Abstract: Publication date: Available online 2 January 2018
      Source:Archives of Biochemistry and Biophysics
      Author(s): Brian B. Hasinoff
      Bortezomib, carfilzomib, ixazomib, oprozomib, and delanzomib are anticancer drugs that target the proteasomal system. Carfilzomib and oprozomib are epoxyketones that form an irreversible covalent bond with the 20S proteasome, whereas bortezomib, ixazomib, and delanzomib are boronic acids that form slowly reversible adducts. The binding kinetics of some of these drugs have either not been well characterized, or have been studied under a variety of different conditions. Utilizing a fluorogenic substrate the kinetics of the slow-binding inhibition of the chymotrypsin-like proteasomal activity of human 20S proteasome was determined under a standard set of conditions in order to compare the kinetic and equilibrium properties of these drugs. Progress curve analysis was used to obtain second order on and first-order off rate constants, and equilibrium- and kinetically-determined inhibitor dissociation constants. Oprozomib inhibited the 20S proteasome with a second-order binding on rate constant that was 60-fold slower than for ixazomib, the fastest binding drug. Delanzomib dissociated from its complex with the 20S proteasome with a half-time that was more than 20-fold slower than for ixazomib, the fastest dissociating drug. The differences in the binding and the dissociation of these drugs may, in part, explain some of their pharmacological and toxicological properties.

      PubDate: 2018-01-04T02:09:13Z
      DOI: 10.1016/j.abb.2017.12.020
       
  • A single amino acid residue regulates the substrate affinity and
           specificity of indoleamine 2,3-dioxygenase
    • Authors: Hajime J. Yuasa; Mayumi Sugiura; Terue Harumoto
      Abstract: Publication date: Available online 28 December 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Hajime J. Yuasa, Mayumi Sugiura, Terue Harumoto
      Indoleamine 2,3-dioxygenase (IDO) is a heme-containing enzyme that catalyses the oxidative cleavage of L-Trp. The ciliate Blepharisma stoltei has four IDO genes (IDO-I, -II, -III and -IV), which seem to have evolved via two sequential gene duplication events. Each IDO enzyme has a distinct enzymatic property, where IDO-III ha–s a high affinity for L-Trp, whereas the affinity of the other three isoforms for L-Trp is low. IDO-I also exhibits a significant catalytic activity with another indole compound: 5-hydroxy-L-tryptophan (5-HTP). IDO-I is considered to be an enzyme that is involved in the biosynthesis of the 5-HTP-derived mating pheromone, gamone 2. By analysing a series of chimeric enzymes based on extant and predicted ancestral enzymes, we identified Asn131 in IDO-I and Glu132 in IDO-III as the key residues responsible for their high affinity for each specific substrate. These two residues were aligned in an identical position as the substrate-determining residue (SDR). Thus, the substrate affinity and specificity are regulated mostly by a single amino acid residue in the Blepharisma IDO-I and IDO-III enzymes.

      PubDate: 2018-01-04T02:09:13Z
      DOI: 10.1016/j.abb.2017.12.019
       
  • Phosphorylation of Ser-525 in βPix impairs Nox1-activating ability in
           Caco-2 cells
    • Authors: Yuuki Kaito; Ryosuke Kataoka; Tatsuya Mihara; Kento Takechi; Akira Takahira; Shuhei Watanabe; Fei Han; Minoru Tamura
      Abstract: Publication date: Available online 11 December 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yuuki Kaito, Ryosuke Kataoka, Tatsuya Mihara, Kento Takechi, Akira Takahira, Shuhei Watanabe, Fei Han, Minoru Tamura
      βPix activates Nox1, an O2 −-generating NADPH oxidase, through Rac activation. In this study, we found that S525E mutation of βPix eliminated its Nox1-activating ability in transfected Caco-2 cells. Unexpectedly, affinity for Rac was not diminished but rather enhanced by S525E mutation, and guanine nucleotide exchange factor (GEF) activity was not altered. The N-terminal fragment (amino acids 1–400) showed similar Rac-binding and GEF activity to wild-type βPix. In contrast, the C-terminal fragment (amino acids 408–646) had higher Rac-binding activity, particularly for Rac-GTP, than wild-type βPix, and showed no GEF activity. These data suggest that a second Rac-binding site within the C-terminal region is opened by phosphorylation of Ser-525. The site may bind not only Rac-GDP but also Rac-GTP released from the N-terminal catalytic region, which interrupts Rac-GTP translocation to the membrane where Nox1 resides. If one considers that S340E mutation enhances Nox1 activation (Kaito et al., 2014), the present study suggests that βPix can also play an inhibitory role in O2 − production, depending on the sites of phosphorylation.
      Graphical abstract image

      PubDate: 2018-01-04T02:09:13Z
      DOI: 10.1016/j.abb.2017.12.010
       
  • Interdependence of GLO I and PKM2 in the Metabolic shift to escape
           apoptosis in GLO I-dependent cancer cells
    • Authors: Nami Shimada; Ryoko Takasawa; Sei-ichi Tanuma
      Pages: 1 - 7
      Abstract: Publication date: 15 January 2018
      Source:Archives of Biochemistry and Biophysics, Volume 638
      Author(s): Nami Shimada, Ryoko Takasawa, Sei-ichi Tanuma
      Many cancer cells undergo metabolic reprogramming known as the Warburg effect, which is characterized by a greater dependence on glycolysis for ATP generation, even under normoxic conditions. Glyoxalase I (GLO I) is a rate-limiting enzyme involved in the detoxification of cytotoxic methylglyoxal formed in glycolysis and which is known to be highly expressed in many cancer cells. Thus, specific inhibitors of GLO I are expected to be effective anticancer drugs. We previously discovered a novel GLO I inhibitor named TLSC702. Although the strong inhibitory activity of TLSC702 was observed in the in vitro enzyme assay, higher concentrations were required to induce apoptosis at the cellular level. One of the proposed reasons for this difference is that cancer cells alter the energy metabolism leading them to become more dependent on mitochondrial respiration than glycolysis (Metabolic shift) to avoid apoptosis induction. Thus, we assumed that combination of TLSC702 with shikonin—a specific inhibitor of pyruvate kinase M2 (PKM2) that acts as a driver of TCA cycle by supplying pyruvate and which is known to be specifically expressed in cancer cells—would have anticancer effects. We herein show the anticancer effects of combination treatment with TLSC702 and shikonin, and a possible anticancer mechanism.
      Graphical abstract image

      PubDate: 2017-12-13T00:01:13Z
      DOI: 10.1016/j.abb.2017.12.008
      Issue No: Vol. 638 (2017)
       
  • Molecular cloning and functional characterization of three terpene
           synthases from unripe fruit of black pepper (Piper nigrum)
    • Authors: Zhehao Jin; Moonhyuk Kwon; Ah-Reum Lee; Dae-Kyun Ro; Juraithip Wungsintaweekul; Soo-Un Kim
      Pages: 35 - 40
      Abstract: Publication date: 15 January 2018
      Source:Archives of Biochemistry and Biophysics, Volume 638
      Author(s): Zhehao Jin, Moonhyuk Kwon, Ah-Reum Lee, Dae-Kyun Ro, Juraithip Wungsintaweekul, Soo-Un Kim
      To identify terpene synthases (TPS) responsible for the biosynthesis of the sesquiterpenes that contribute to the characteristic flavors of black pepper (Piper nigrum), unripe peppercorn was subjected to the Illumina transcriptome sequencing. The BLAST analysis using amorpha-4,11-diene synthase as a query identified 19 sesquiterpene synthases (sesqui-TPSs), of which three full-length cDNAs (PnTPS1 through 3) were cloned. These sesqui-TPS cDNAs were expressed in E. coli to produce recombinant enzymes for in vitro assays, and also expressed in the engineered yeast strain to assess their catalytic activities in vivo. PnTPS1 produced β-caryophyllene as a main product and humulene as a minor compound, and thus was named caryophyllene synthase (PnCPS). Likewise, PnTPS2 and PnTPS3 were, respectively, named cadinol/cadinene synthase (PnCO/CDS) and germacrene D synthase (PnGDS). PnGDS expression in yeast yielded β-cadinene and α-copaene, the rearrangement products of germacrene D. Their k cat/K m values (20–37.7 s−1 mM−1) were comparable to those of other sesqui-TPSs. Among three PnTPSs, the transcript level of PnCPS was the highest, correlating with the predominant β-caryophyllene biosynthesis in the peppercorn. The products and rearranged products of three PnTPSs could account for about a half of the sesquiterpenes in number found in unripe peppercorn.
      Graphical abstract image

      PubDate: 2017-12-24T00:38:03Z
      DOI: 10.1016/j.abb.2017.12.011
      Issue No: Vol. 638 (2017)
       
  • Intraspecific variation of Centruroides sculpturatus scorpion venom from
           two regions of Arizona
    • Authors: Edson Norberto Carcamo-Noriega; Timoteo Olamendi-Portugal; Rita Restano-Cassulini; Ashlee Rowe; Selene Jocelyn Uribe-Romero; Baltazar Becerril; Lourival Domingos Possani
      Pages: 52 - 57
      Abstract: Publication date: 15 January 2018
      Source:Archives of Biochemistry and Biophysics, Volume 638
      Author(s): Edson Norberto Carcamo-Noriega, Timoteo Olamendi-Portugal, Rita Restano-Cassulini, Ashlee Rowe, Selene Jocelyn Uribe-Romero, Baltazar Becerril, Lourival Domingos Possani
      This study investigated geographic variability in the venom of Centruroides sculpturatus scorpions from different biotopes. Venom from scorpions collected from two different regions in Arizona; Santa Rita Foothills (SR) and Yarnell (Yar) were analyzed. We found differences between venoms, mainly in the two most abundant peptides; SR (CsEv2e and CsEv1f) and Yar (CsEv2 and CsEv1c) identified as natural variants of CsEv1 and CsEv2. Sequence analyses of these peptides revealed conservative amino acid changes between variants, which may underlie biological activity against arthropods. A third peptide (CsEv6) was highly abundant in the Yar venom compared to the SR venom. CsEv6 is a 67 amino acid peptide with 8 cysteines. CsEv6 did not exhibit toxicity to the three animal models tested. However, both venoms shared similarities in peptides that are predicted to deter predators. For example, both venoms expressed CsEI (lethal to chick) in similar abundance, while CsEd and CsEM1a (toxic to mammals) displayed only moderate variation in their abundance. Electrophysiological evaluation of CsEd and CsEM1a showed that both toxins act on the human sodium-channel subtype 1.6 (hNav 1.6). Complete sequencing revealed that both toxins are structurally similar to beta-toxins isolated from different Centruroides species that also target hNav 1.6.

      PubDate: 2017-12-24T00:38:03Z
      DOI: 10.1016/j.abb.2017.12.012
      Issue No: Vol. 638 (2017)
       
  • Kinetics and thermodynamics of the thermal inactivation and chaperone
           assisted folding of zebrafish dihydrofolate reductase
    • Authors: Charu Thapliyal; Neha Jain; Naira Rashid; Pratima Chaudhuri (Chattopadhyay)
      Pages: 21 - 30
      Abstract: Publication date: 1 January 2018
      Source:Archives of Biochemistry and Biophysics, Volume 637
      Author(s): Charu Thapliyal, Neha Jain, Naira Rashid, Pratima Chaudhuri (Chattopadhyay)
      The maintenance of thermal stability is a major issue in protein engineering as many proteins tend to form inactive aggregates at higher temperatures. Zebrafish DHFR, an essential protein for the survival of cells, shows irreversible thermal unfolding transition. The protein exhibits complete unfolding and loss of activity at 50 °C as monitored by UV-Visible, fluorescence and far UV-CD spectroscopy. The heat induced inactivation of zDHFR follows first–order kinetics and Arrhenius law. The variation in the value of inactivation rate constant, k with increasing temperatures depicts faster inactivation at elevated temperatures. We have attempted to study the chaperoning ability of a shorter variant of GroEL (minichaperone) and compared it with that of conventional GroEL-GroES chaperone system. Both the chaperone system prevented the aggregation and assisted in refolding of zDHFR. The rate of thermal inactivation was significantly retarded in the presence of chaperones which indicate that it enhances the thermal stability of the enzyme. As minichaperone is less complex, and does not require high energy co-factors like ATP, for its function as compared to conventional GroEL-GroES system, it can act as a very good in vitro as well as in vivo chaperone model for monitoring assisted protein folding phenomenon.

      PubDate: 2017-12-24T00:38:03Z
      DOI: 10.1016/j.abb.2017.11.006
      Issue No: Vol. 637 (2017)
       
  • Eucalyptus globulus extract protects against UVB-induced photoaging by
           enhancing collagen synthesis via regulation of TGF-β/Smad signals and
           attenuation of AP-1
    • Authors: Bom Park; Eunson Hwang; Seul A. Seo; Jin-Gyeong Cho; Jung-Eun Yang; Tae-Hoo Yi
      Pages: 31 - 39
      Abstract: Publication date: 1 January 2018
      Source:Archives of Biochemistry and Biophysics, Volume 637
      Author(s): Bom Park, Eunson Hwang, Seul A. Seo, Jin-Gyeong Cho, Jung-Eun Yang, Tae-Hoo Yi
      UV irradiation triggers the overproduction of matrix metalloproteinases and collagen degradation, which in turn causes increased pigmentation, dryness, and deep wrinkling of the skin. These chronic symptoms are collectively referred to as photoaging. Eucalyptus globulus is an evergreen tree that is widely used in cosmetics because of its antimicrobial activity. In this study, we investigated the protective effect of 50% ethanol extracts of Eucalyptus globulus on UV-induced photoaging in vitro and in vivo. Normal human dermal fibroblasts were treated with Eucalyptus globulus at concentrations ranging from 1 to 100 μg/mL after UVB or non-UVB irradiation. We found that Eucalyptus globulus suppressed the expression of MMPs and IL-6, but increased the expression of TGF-β1 and procollagen type 1. In addition, Eucalyptus globulus inhibited activation of the AP-1 transcription factor, an inducer of MMPs. Eucalyptus globulus was also found to regulate TGF-β/Smad signaling by reversing the activity of negative Smad regulators. Lastly, in vivo studies showed that topical application of Eucalyptus globulus on UVB-irradiated hairless mice reduced wrinkle formation and dryness by down-regulating MMP-1 and up-regulating expression of elastin, TGF-β1, and procollagen type 1. Taken together, these data suggest that Eucalyptus globulus may be a useful agent in cosmetic products.
      Graphical abstract image

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/j.abb.2017.11.007
      Issue No: Vol. 637 (2017)
       
  • Cardiotonic actions of quercetin and its metabolite tamarixetin through a
           digitalis-like enhancement of Ca2+ transients
    • Authors: Kengo Hayamizu; Sachio Morimoto; Miki Nonaka; Sumio Hoka; Toshiyuki Sasaguri
      Pages: 40 - 47
      Abstract: Publication date: 1 January 2018
      Source:Archives of Biochemistry and Biophysics, Volume 637
      Author(s): Kengo Hayamizu, Sachio Morimoto, Miki Nonaka, Sumio Hoka, Toshiyuki Sasaguri
      The plant-derived flavonoid, quercetin (QCT), has many biological actions, including cardioprotective actions, resulting from its antioxidant and anti-inflammatory effects. In this study, effects of QCT and its metabolites on the contraction and Ca2+ transients (CaT) of mouse single cardiomyocytes were simultaneously measured and compared with those of isoproterenol and digoxin. Furthermore, cardiac function and plasma concentrations were analyzed after bolus intravenous administration of QCT in mice. QCT and its metabolite, tamarixetin, as well as isoproterenol and digoxin, enhanced the contraction and CaT of cardiomyocytes. The inotropic action of isoproterenol was accompanied by an increase in the velocities of sarcomere shortening and relengthening and CaT decay through activation of cAMP-dependent protein kinase; however, no such lusitropic effects accompanied the inotropic action of QCT, tamarixetin or digoxin. Intravenous administration of QCT to mice resulted in a sustained increase in cardiac systolic function; QCT was rapidly metabolized to tamarixetin and its plasma concentration was maintained at high levels over a similar time frame as the enhancement of cardiac systolic function. These results suggest that QCT exerts a cardiotonic action in vivo at least, in part, through digitalis-like enhancement of CaT by itself and its metabolite tamarixetin.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/j.abb.2017.11.009
      Issue No: Vol. 637 (2017)
       
  • MiR-429 regulates the metastasis and EMT of HCC cells through targeting
           RAB23
    • Authors: Hongyan Xue; Guo-Yan Tian
      Pages: 48 - 55
      Abstract: Publication date: 1 January 2018
      Source:Archives of Biochemistry and Biophysics, Volume 637
      Author(s): Hongyan Xue, Guo-Yan Tian
      Accumulating documents have revealed that microRNAs (miRNAs) play critical roles in the development and progression of tumors. MiR-429 has been reported to be involved in regulating various cellular processes. However, its biological role and underlying mechanism in hepatocellular carcinoma (HCC) still need to be further studied. The present study aimed to investigate the function of miR-429 in the progression of HCC. In terms of this paper, it was found that miR-429 was down-regulated in HCC tissues and cells. After being transfected with miR-429 mimics, miR-429 decreased the migratory capacity and reversed the EMT to MET in HCC cells. RAB23 was confirmed as a target of miR-429. Rescue assays further verified that the function of miR-429 in HCC cells was exerted through targeting RAB23. In general, it was concluded that the signal pathway miR-429/RAB23 might be a potential target for HCC treatment.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/j.abb.2017.11.011
      Issue No: Vol. 637 (2017)
       
  • Naringin prevents bone loss in a rat model of type 1 Diabetes mellitus
    • Authors: M. Rivoira; V. Rodríguez; G. Picotto; R. Battaglino; N. Tolosa de Talamoni
      Pages: 56 - 63
      Abstract: Publication date: 1 January 2018
      Source:Archives of Biochemistry and Biophysics, Volume 637
      Author(s): M. Rivoira, V. Rodríguez, G. Picotto, R. Battaglino, N. Tolosa de Talamoni
      The aim of this work was to know whether naringin (NA) could prevent the bone complications in a model of streptozotocin (STZ) induced diabetes. Rats were divided in: 1) controls, 2) STZ-rats, 3) STZ-rats treated with 40 mg NA/kg, and 4) STZ-rats treated with 80 mg NA/kg. BMD and BMC were performed by DEXA. Bone histomorphometry and histology as well as TRAP staining were done in tibia. Osteocalcin (OCN) was determined in bone and serum. Glutathione content and SOD and catalase activities were assayed in bone marrow from femur. The data showed that NA80 increased the BMD and BMC from the long bones of STZ-rats. Both NA40 and NA80 normalized the trabecular number and the trabecular separations. An increase in the number of adipocytes and TRAP(+) cells in tibia from STZ-rats was blocked by NA. NA40 treatment increased the number of OCN(+) cells, but only the NA80 treatment allowed to reach the control values. NA normalized the SOD and catalase activities in bone marrow of femur from STZ-rats. In conclusion, NA avoids alterations in the physical properties and microstructure of bone from STZ-rats probably by stimulation of osteoblastogenesis, inhibition of the osteoclastogenesis and adipogenesis via blocking the oxidative stress.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/j.abb.2017.12.001
      Issue No: Vol. 637 (2017)
       
  • Atorvastatin affects negatively respiratory function of isolated
           endothelial mitochondria
    • Authors: Izabela Broniarek; Wieslawa Jarmuszkiewicz
      Pages: 64 - 72
      Abstract: Publication date: 1 January 2018
      Source:Archives of Biochemistry and Biophysics, Volume 637
      Author(s): Izabela Broniarek, Wieslawa Jarmuszkiewicz
      The purpose of this research was to elucidate the direct effects of two popular blood cholesterol-lowering drugs used to treat cardiovascular diseases, atorvastatin and pravastatin, on respiratory function, membrane potential, and reactive oxygen species formation in mitochondria isolated from human umbilical vein endothelial cells (EA.hy926 cell line). Hydrophilic pravastatin did not significantly affect endothelial mitochondria function. In contrast, hydrophobic calcium-containing atorvastatin induced a loss of outer mitochondrial membrane integrity, an increase in hydrogen peroxide formation, and reductions in maximal (phosphorylating or uncoupled) respiratory rate, membrane potential and oxidative phosphorylation efficiency. The atorvastatin-induced changes indicate an impairment of mitochondrial function at the level of ATP synthesis and at the level of the respiratory chain, likely at complex I and complex III. The atorvastatin action on endothelial mitochondria was highly dependent on calcium ions and led to a disturbance in mitochondrial calcium homeostasis. Uptake of calcium ions included in atorvastatin molecule induced mitochondrial uncoupling that enhanced the inhibition of the mitochondrial respiratory chain by atorvastatin. Our results indicate that hydrophobic calcium-containing atorvastatin, widely used as anti-atherosclerotic agent, has a direct negative action on isolated endothelial mitochondria.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/j.abb.2017.12.003
      Issue No: Vol. 637 (2017)
       
  • Effect of quercetin on cell protection via erythropoietin and cell injury
           of HepG2 cells
    • Authors: Kazuhiko Nishimura; Risa Matsumoto; Yuuki Yonezawa; Hiroshi Nakagawa
      Pages: 11 - 16
      Abstract: Publication date: 15 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 636
      Author(s): Kazuhiko Nishimura, Risa Matsumoto, Yuuki Yonezawa, Hiroshi Nakagawa
      Quercetin is a flavonoid that has roles in both cytoprotection and cytotoxicity. The relation of queretin's cytoprotective and cytotoxic effects are unknown. Quercetin has been shown to induce expression of hypoxia-inducible factor, a protein that is known to regulate transcription of the erythropoietin (EPO) gene, and EPO is known to have a cytoprotective effect. This study used HepG2 cells to assess whether the cell-protective and/or cytotoxic roles of quercetin are mediated by promotion of EPO production. Increases in the levels of HIF-1α protein and EPO mRNA were quercetin concentration-dependent, with significant increases observed from 10 μM quercetin. Silencing of EPO expression by si-EPO RNA attenuated quercetin-induced cytoprotection against hydrogen peroxide toxicity. Cytotoxicity, evidenced by the induction of apoptosis, was significantly increased by exposure to 50 μM quercetin. Specifically, the levels of cleaved caspase-3 and Bax and the rate of cell death increased, and the level of Bcl-2 decreased, in cells treated with 50 μM quercetin. In contrast, exposure to 10 μM quercetin attenuated cisplatin-induced apoptosis. However, quercetin's ability to protect cells from cisplatin-induced apoptosis was eliminated when EPO expression was silenced using si-EPO RNA. Together, these results suggested that quercetin's cytoprotective effects in HepG2 cells are mediated via EPO production.

      PubDate: 2017-11-08T15:55:15Z
      DOI: 10.1016/j.abb.2017.10.013
      Issue No: Vol. 636 (2017)
       
  • One single salt bridge explains the different cytolytic activities shown
           by actinoporins sticholysin I and II from the venom of Stichodactyla
           helianthus
    • Authors: Esperanza Rivera-de-Torre; Juan Palacios-Ortega; Sara García-Linares; José G. Gavilanes; Álvaro Martínez-del-Pozo
      Pages: 79 - 89
      Abstract: Publication date: Available online 11 November 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Esperanza Rivera-de-Torre, Juan Palacios-Ortega, Sara García-Linares, José G. Gavilanes, Álvaro Martínez-del-Pozo
      Sticholysins I and II (StnI and StnII), α-pore forming toxins from the sea anemone Stichodactyla helianthus, are water-soluble toxic proteins which upon interaction with lipid membranes of specific composition bind to the bilayer, extend and insert their N-terminal α-helix, and become oligomeric integral membrane structures. The result is a pore that leads to cell death by osmotic shock. StnI and StnII show 93% of sequence identity, but also different membrane pore-forming activities. The hydrophobicity profile along the first 18 residues revealed differences which were canceled by substituting StnI amino acids 2 and 9. Accordingly, the StnID9A mutant, and the corresponding StnIE2AD9A variant, showed enhanced hemolytic activity. They also revealed a key role for an exposed salt bridge between Asp9 and Lys68. This interaction is not possible in StnII but appears conserved in the other two well-characterized actinoporins, equinatoxin II and fragaceatoxin C. The StnII mutant A8D showed that this single replacement was enough to transform StnII into a version with impaired pore-forming activity. Overall, the results show the key importance of this salt bridge linking the N-terminal stretch to the β-sandwich core. A conclusion of general application for the understanding of salt bridges role in protein design, folding and stability.
      Graphical abstract image

      PubDate: 2017-11-15T16:22:32Z
      DOI: 10.1016/j.abb.2017.11.005
      Issue No: Vol. 636 (2017)
       
  • Regulation of glutamate dehydrogenase (GDH) in response to whole body
           freezing in wood frog liver linked to differential acetylation and
           ADP-ribosylation
    • Authors: Stuart R. Green; Kenneth B. Storey
      Pages: 90 - 99
      Abstract: Publication date: 15 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 636
      Author(s): Stuart R. Green, Kenneth B. Storey
      Glutamate dehydrogenase (GDH) represents a critical enzyme catalyzing the reaction spanning amino acid catabolism, the Krebs cycle, and urea production in the wood frog. GDH breaks down glutamate and NAD+ to generate α-ketoglutaric acid (α-KG), NADH and ammonium that can be metabolized to form urea. Purification of GDH from control and frozen male wood frog livers was performed using a two-step column chromatography procedure with a cation exchange column and a GTP-agarose affinity column. Analysis of kinetic parameters of the purified GDH showed several notable differences between the control and stress. Under standard assay conditions, the affinity of GDH for its substrates was significantly higher for the freeze-exposed enzyme than for the control (glutamate Km: 41% decrease, NAD+ Km: 40% decrease). The maximal activity for the control enzyme was also noted to be lower than the frozen. This suggests that the frozen form of the GDH was activated relative to the control form. Western blot analysis of common posttranslational modifications indicated that the frozen enzyme had a lower degree of acetylation and ADP-ribosylation than its control counterpart. These results suggest that GDH is regulated in the wood frog liver by means of altering post-translational modifications in response to freezing.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/j.abb.2017.10.010
      Issue No: Vol. 636 (2017)
       
  • Acetyl-CoA carboxylase from Escherichia coli exhibits a pronounced
           hysteresis when inhibited by palmitoyl-acyl carrier protein
    • Authors: Alexandra Evans; Wendy Ribble; Erin Schexnaydre; Grover L. Waldrop
      Pages: 100 - 109
      Abstract: Publication date: 15 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 636
      Author(s): Alexandra Evans, Wendy Ribble, Erin Schexnaydre, Grover L. Waldrop
      Acetyl-CoA carboxylase (ACC) in bacteria is composed of three components: biotin carboxylase, biotin carboxyl carrier protein, and carboxyltransferase. ACC catalyzes the first committed step in fatty acid synthesis: the carboxylation of acetyl-CoA to form malonyl-CoA via a two-step reaction. In the first half-reaction, biotin carboxylase catalyzes the ATP-dependent carboxylation of the vitamin biotin covalently linked to biotin carboxyl carrier protein. In the second half-reaction, the carboxyl group is transferred from biotin to acetyl-CoA by the enzyme carboxyltransferase, to form malonyl-CoA. In most Gram-negative and Gram-positive bacteria, the three components of ACC form a complex that requires communication for catalysis, and is subject to feedback inhibition by acylated-acyl carrier proteins. This study investigated the mechanism of inhibition of palmitoyl-acyl carrier protein (PACP) on ACC. Unexpectedly, ACC was found to exhibit a significant hysteresis, meaning ACC was subject to inhibition by PACP in a time dependent manner. Pull-down assays demonstrated PACP does not prevent formation of the multiprotein complex, while steady-state kinetic analyses showed PACP inhibited ACC activity allosterically. Structure-activity analyses revealed that the pantothenic acid moiety of PACP is responsible for the inhibition of ACC. This study provides the first evidence of the hysteretic nature of ACC.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/j.abb.2017.10.016
      Issue No: Vol. 636 (2017)
       
  • Silencing of Glut1 induces chemoresistance via modulation of
           Akt/GSK-3β/β-catenin/survivin signaling pathway in breast cancer cells
    • Authors: Sunhwa Oh; Hyungjoo Kim; KeeSoo Nam; Incheol Shin
      Pages: 110 - 122
      Abstract: Publication date: 15 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 636
      Author(s): Sunhwa Oh, Hyungjoo Kim, KeeSoo Nam, Incheol Shin
      Cancer cells require increased aerobic glycolysis to support rapid cell proliferation. For their increased energy demands, cancer cells express glucose transporter (Glut) proteins at a high level. Glut1 is associated with basal-like breast cancer and is considered a potential therapeutic target. To investigate the possibility of Glut1 as a therapeutic target in breast cancer cells, we downregulated Glut1 in triple-negative breast cancer (TNBC) cell lines using a short hairpin system. We determined whether Glut1 silencing might enhance anti-proliferative effect of chemotherapeutic agents. Contrary to our hypothesis, ablation of Glut1 attenuated apoptosis and increased drug resistance via upregulation of p-Akt/p-GSK-3β (Ser9)/β-catenin/survivin. These results indicated that the potential of Glut1 as a therapeutic target should be carefully reevaluated.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/j.abb.2017.08.009
      Issue No: Vol. 636 (2017)
       
  • Insights on the conformational dynamics of human frataxin through
           modifications of loop-1
    • Authors: Martín E. Noguera; Martín Aran; Clara Smal; Diego S. Vazquez; María Georgina Herrera; Ernesto A. Roman; Nadine Alaimo; Mariana Gallo; Javier Santos
      Pages: 123 - 137
      Abstract: Publication date: 15 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 636
      Author(s): Martín E. Noguera, Martín Aran, Clara Smal, Diego S. Vazquez, María Georgina Herrera, Ernesto A. Roman, Nadine Alaimo, Mariana Gallo, Javier Santos
      Human frataxin (FXN) is a highly conserved mitochondrial protein involved in iron homeostasis and activation of the iron-sulfur cluster assembly. FXN deficiency causes the neurodegenerative disease Friedreich's Ataxia. Here, we investigated the effect of alterations in loop-1, a stretch presumably essential for FXN function, on the conformational stability and dynamics of the native state. We generated four loop-1 variants, carrying substitutions, insertions and deletions. All of them were stable and well-folded proteins. Fast local motions (ps-ns) and slower long-range conformational dynamics (μs-ms) were altered in some mutants as judged by NMR. Particularly, loop-1 modifications impact on the dynamics of a distant region that includes residues from the β-sheet, helix α1 and the C-terminal. Remarkably, all the mutants retain the ability to activate cysteine desulfurase, even when two of them exhibit a strong decrease in iron binding, revealing a differential sensitivity of these functional features to loop-1 perturbation. Consequently, we found that even for a small and relatively rigid protein, engineering a loop segment enables to alter conformational dynamics through a long-range effect, preserving the native-state structure and important aspects of function.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/j.abb.2017.10.022
      Issue No: Vol. 636 (2017)
       
  • GADD45 family proteins suppress JNK signaling by targeting MKK7
    • Authors: Takumi Ueda; Yuri Kohama; Ayana Kuge; Eriko Kido; Hiroshi Sakurai
      Pages: 1 - 7
      Abstract: Publication date: Available online 14 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Takumi Ueda, Yuri Kohama, Ayana Kuge, Eriko Kido, Hiroshi Sakurai
      Growth arrest and DNA damage-inducible 45 (GADD45) family genes encode related proteins, including GADD45α, GADD45β, and GADD45γ. In HeLa cells, expression of GADD45 members is differentially regulated under a variety of environmental conditions, but thermal and genotoxic stresses induce the expression of all genes. The heat shock response of GADD45β is mediated by the heat shock transcription factor 1 (HSF1), and GADD45β is necessary for heat stress survival. Heat and genotoxic stress-induced activation of c-Jun N-terminal kinase (JNK) is suppressed by the expression of GADD45 proteins. GADD45 proteins bind the JNK kinase mitogen-activated protein kinase kinase 7 (MKK7) and inhibit its activity, even under normal physiological conditions. Our findings indicate that GADD45 essentially suppresses the MKK7-JNK pathway and suggest that differentially expressed GADD45 family members fine-tune stress-inducible JNK activity.

      PubDate: 2017-10-14T08:31:24Z
      DOI: 10.1016/j.abb.2017.10.005
      Issue No: Vol. 635 (2017)
       
  • Genotoxic effect and antigen binding characteristics of SLE
           auto-antibodies to peroxynitrite-modified human DNA
    • Authors: Md Asad Khan; Khursheed Alam; Syed Hassan Mehdi; M. Moshahid A. Rizvi
      Pages: 8 - 16
      Abstract: Publication date: 1 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 635
      Author(s): Md Asad Khan, Khursheed Alam, Syed Hassan Mehdi, M. Moshahid A. Rizvi
      Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by auto-antibodies against native deoxyribonucleic acid after modification and is one of the reasons for the development of SLE. Here, we have evaluated the structural perturbations in human placental DNA by peroxynitrite using spectroscopy, thermal denaturation and high-performance liquid chromatography (HPLC). Peroxynitrite is a powerful potent bi-functional oxidative/nitrative agent that is produced both endogenously and exogenously. In experimental animals, the peroxynitrite-modified DNA was found to be highly immunogenic. The induced antibodies showed cross-reactions with different types of DNA and nitrogen bases that were modified with peroxynitrite by inhibition ELISA. The antibody activity was inhibited by approximately 89% with its immunogen as the inhibitor. The antigen-antibodies interaction between induced antibodies with peroxynitrite-modified DNA showed retarded mobility as compared to the native form. Furthermore, significantly increased binding was also observed in SLE autoantibodies with peroxynitrite-modified DNA than native form. Moreover, DNA isolated from lymphocyte of SLE patients revealed significant recognition of anti-peroxynitrite-modified DNA immunoglobulin G (IgG). Our data indicates that DNA modified with peroxynitrite presents unique antigenic determinants that may induce autoantibody response in SLE.

      PubDate: 2017-10-26T07:19:33Z
      DOI: 10.1016/j.abb.2017.10.008
      Issue No: Vol. 635 (2017)
       
  • Sex-dependent impact of Scp-2/Scp-x gene ablation on hepatic phytol
           metabolism
    • Authors: Avery L. McIntosh; Stephen M. Storey; Huan Huang; Ann B. Kier; Friedhelm Schroeder
      Pages: 17 - 26
      Abstract: Publication date: 1 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 635
      Author(s): Avery L. McIntosh, Stephen M. Storey, Huan Huang, Ann B. Kier, Friedhelm Schroeder
      While prior studies focusing on male mice suggest a role for sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x; DKO) on hepatic phytol metabolism, its role in females is unresolved. This issue was addressed using female and male wild-type (WT) and DKO mice fed a phytoestrogen-free diet without or with 0.5% phytol. GC/MS showed that hepatic: i) phytol was absent and its branched-chain fatty acid (BCFA) metabolites were barely detectable in WT control-fed mice; ii) accumulation of phytol as well as its peroxisomal metabolite BCFAs (phytanic acid » pristanic and 2,3-pristenic acids) was increased by dietary phytol in WT females, but only slightly in WT males; iii) accumulation of phytol and BCFA was further increased by DKO in phytol-fed females, but much more markedly in males. Livers of phytol-fed WT female mice as well as phytol-fed DKO female and male mice also accumulated increased proportion of saturated straight-chain fatty acids (LCFA) at the expense of unsaturated LCFA. Liver phytol accumulation was not due to increased SCP-2 binding/transport of phytol since SCP-2 bound phytanic acid, but not its precursor phytol. Thus, the loss of Scp-2/Scp-x contributed to a sex-dependent hepatic accumulation of dietary phytol and BCFA.
      Graphical abstract image

      PubDate: 2017-10-26T07:19:33Z
      DOI: 10.1016/j.abb.2017.10.011
      Issue No: Vol. 635 (2017)
       
  • Dielectric properties of plasma membrane: A signature for dyslipidemia in
           diabetes mellitus
    • Authors: Kakali Ghoshal; Subhadip Chakraborty; Chirantan Das; Sanatan Chattopadhyay; Subhankar Chowdhury; Maitree Bhattacharyya
      Pages: 27 - 36
      Abstract: Publication date: 1 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 635
      Author(s): Kakali Ghoshal, Subhadip Chakraborty, Chirantan Das, Sanatan Chattopadhyay, Subhankar Chowdhury, Maitree Bhattacharyya
      Dielectric properties of a living biological membrane play crucial role indicating the status of the cell in pathogenic or healthy condition. A distinct variation in membrane capacitance and impedance was observed for peripheral blood mononuclear cell (PBMC) suspensions for diabetic and diabetic-dyslipidemic subjects compared to healthy control. Low frequency region were explicitly considered in electrical analysis to address complex membrane dielectric factors that alter the system capacitance of a PBMC suspension. Such variation was marked in size, morphology and membrane function of PBMCs for control and diseased cases. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) studies reveal significant alteration in surface morphology of PBMCs in diseased condition. Side scatter of flow cytometry reveals complexity of PBMCs in diseased condition. Changes in size between groups were not found by SEM and forward scatter. Functional alteration in PBMCs was manifested by significant changes in cell membrane properties like Na+, K+ ATPase and Ca2+, Mg2+ ATPase activity, reduced plasma membrane fluidity and changes in intracellular Ca2+ content, which bear significant correlation in diabetic and diabetic dyslipidemic subjects. Therefore, dielectric parameters of PBMCs in diabetic-dyslipidemic challenges may led to interesting correlation opening the possibility of identifying crucial signature biomarkers.

      PubDate: 2017-11-02T08:27:27Z
      DOI: 10.1016/j.abb.2017.10.002
      Issue No: Vol. 635 (2017)
       
  • Raman spectroscopy reveals the lipid phase transition in preimplantation
           mouse embryos during freezing
    • Authors: K.A. Okotrub; S.Y. Amstislavsky; N.V. Surovtsev
      Pages: 37 - 43
      Abstract: Publication date: 1 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 635
      Author(s): K.A. Okotrub, S.Y. Amstislavsky, N.V. Surovtsev
      Although lipid phase transition is believed to be among the major damaging factors in oocytes and preimplantation embryos cryopreservation, lack of the appropriate experimental methods limits investigation of this phenomenon. Herein, we demonstrate the capabilities of Raman spectroscopy to detect the lipid phase transition within the freezing preimplantation mouse embryos. We exploit the sensibility of antisymmetric CH2 Raman peak to the phase state of lipids. It is shown that during the freezing of the mouse embryos the lipid phase transition occurs at the temperatures between −7 and 0 °C. Similar temperature dependences of CH2 mode intensities are found for lipids in the preimplantation embryos and a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, implying the similarity in the occupation rules of conformational states. Raman spectroscopy is considered as a method of choice to study the lipid phase transition during preimplantation mammalian embryos freezing and cryopreservation.
      Graphical abstract image

      PubDate: 2017-11-02T08:27:27Z
      DOI: 10.1016/j.abb.2017.10.001
      Issue No: Vol. 635 (2017)
       
  • Naringin prevents the inhibition of intestinal Ca2+ absorption induced by
           a fructose rich diet
    • Authors: V.A. Rodríguez; M.A. Rivoira; S. Guizzardi; N.G. Tolosa de Talamoni
      Pages: 299 - 300
      Abstract: Publication date: 15 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 636
      Author(s): V. Rodríguez, M. Rivoira, S. Guizzardi, N. Tolosa de Talamoni
      This study tries to elucidate the mechanisms by which fructose rich diets (FRD) inhibit the rat intestinal Ca2+ absorption, and determine if any or all underlying alterations are prevented by naringin (NAR). Male rats were divided into: 1) controls, 2) treated with FRD, 3) treated with FRD and NAR. The intestinal Ca2+ absorption and proteins of the transcellular and paracellular Ca2+ pathways were measured. Oxidative/nitrosative stress and inflammation parameters were evaluated. FRD rats showed inhibition of the intestinal Ca2+ absorption and decrease in the protein expression of molecules of both Ca2+ pathways, which were blocked by NAR. FRD rats showed an increase in the superoxide anion, a decrease in the glutathione and in the enzymatic activities of the antioxidant system, as well as an increase in the NO content and in the nitrotyrosine content of proteins. They also exhibited an increase in both IL-6 and nuclear NF-κB. All these changes were prevented by NAR. In conclusion, FRD inhibit both pathways of the intestinal Ca2+ absorption due to the oxidative/nitrosative stress and inflammation. Since NAR prevents the oxidative/nitrosative stress and inflammation, it might be a drug to avoid alteration in the intestinal Ca2+ absorption caused by FRD.
      Graphical abstract image

      PubDate: 2017-11-08T15:55:15Z
      DOI: 10.1016/j.bone.2017.03.012
      Issue No: Vol. 105 (2017)
       
  • Acceleration of amyloid fibril formation by carboxyl-terminal truncation
           of human serum amyloid A
    • Authors: Masafumi Tanaka; Toru Kawakami; Nozomi Okino; Kaoru Sasaki; Kiwako Nakanishi; Hiroka Takase; Toshiyuki Yamada; Takahiro Mukai
      Abstract: Publication date: Available online 26 December 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Masafumi Tanaka, Toru Kawakami, Nozomi Okino, Kaoru Sasaki, Kiwako Nakanishi, Hiroka Takase, Toshiyuki Yamada, Takahiro Mukai
      Human serum amyloid A (SAA) is a precursor protein of AA amyloidosis. Although the full-length SAA is 104 amino acids long, the C-terminal-truncated SAA lacking mainly residues 77–104 is predominantly deposited in AA amyloidosis. Nevertheless, the amyloid fibril formation of such truncated forms of human SAA has never been investigated. In the present study, we examined the effect of C-terminal truncation on amyloid fibril formation of human SAA induced by heparan sulfate (HS). Circular dichroism (CD) measurements demonstrated that the C-terminal truncation induces a reduced α-helical structure of the SAA molecule. HS-induced increases in thioflavin T fluorescence for SAA (1–76) peptide and less significant increases for full-length SAA were observed. CD spectral changes of SAA (1–76) peptide but not full-length SAA were observed when incubated with HS, although the spectrum was not typical for a β-structure. Fourier transform infrared experiments clearly revealed that SAA (1–76) peptide forms a β-sheet structure. Transmission electron microscopy revealed that short fibrillar aggregates of SAA (1–76) peptides, which became longer with increasing peptide concentrations, were observed under conditions in which full-length SAA scarcely formed fibrillar aggregates. These results suggested that the C-terminal truncation of human SAA accelerates amyloid fibril formation.

      PubDate: 2017-12-27T00:56:20Z
      DOI: 10.1016/j.abb.2017.12.016
       
  • Hydrophobic interactions of sucralose with protein structures
    • Authors: Nimesh Shukla; Enrico Pomarico; Cody J.S. Hecht; Erika A. Taylor; Majed Chergui; Christina M. Othon
      Abstract: Publication date: Available online 26 December 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Nimesh Shukla, Enrico Pomarico, Cody J.S. Hecht, Erika A. Taylor, Majed Chergui, Christina M. Othon
      Sucralose is a commonly employed artificial sweetener that appears to destabilize protein native structures. This is in direct contrast to the bio-preservative nature of its natural counterpart, sucrose, which enhances the stability of biomolecules against environmental stress. We have further explored the molecular interactions of sucralose as compared to sucrose to illuminate the origin of the differences in their bio-preservative efficacy. We show that the mode of interactions of sucralose and sucrose in bulk solution differ subtly through the use of hydration dynamics measurement and computational simulation. Sucralose does not appear to disturb the native state of proteins for moderate concentrations (<0.2 M) at room temperature. However, as the concentration increases, or in the thermally stressed state, sucralose appears to differ in its interactions with protein leading to the reduction of native state stability. This difference in interaction appears weak. We explored the difference in the preferential exclusion model using time-resolved spectroscopic techniques and observed that both molecules appear to be effective reducers of bulk hydration dynamics. However, the chlorination of sucralose appears to slightly enhance the hydrophobicity of the molecule, which reduces the preferential exclusion of sucralose from the protein-water interface. The weak interaction of sucralose with hydrophobic pockets on the protein surface differs from the behavior of sucrose. We experimentally followed up upon the extent of this weak interaction using isothermal titration calorimetry (ITC) measurements. We propose this as a possible origin for the difference in their bio-preservative properties.
      Graphical abstract image

      PubDate: 2017-12-27T00:56:20Z
      DOI: 10.1016/j.abb.2017.12.013
       
  • Implication of altered ubiquitin-proteasome system and ER stress in the
           muscle atrophy of diabetic rats
    • Authors: S. Sreenivasa Reddy; Karnam Shruthi; Y. Konda Prabhakar; Gummadi Sailaja; G. Bhanuprakash Reddy
      Abstract: Publication date: Available online 24 December 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): S. Sreenivasa Reddy, Karnam Shruthi, Y. Konda Prabhakar, Gummadi Sailaja, G. Bhanuprakash Reddy
      Background Skeletal muscle is adversely affected in type-1 diabetes, and excessively stimulated ubiquitin-proteasome system (UPS) was found to be a leading cause of muscle wasting or atrophy. The role of endoplasmic reticulum (ER) stress in muscle atrophy of type-1 diabetes is not known. Hence, we investigated the role of UPS and ER stress in the muscle atrophy of chronic diabetes rat model. Methods Diabetes was induced with streptozotocin (STZ) in male Sprague-Dawley rats and were sacrificed 2- and 4-months thereafter to collect gastrocnemius muscle. In another experiment, 2-months post-STZ-injection diabetic rats were treated with MG132, a proteasome inhibitor, for the next 2-months and gastrocnemius muscle was collected. Results The muscle fiber cross-sectional area was diminished in diabetic rats. The expression of UPS components: E1, MURF1, TRIM72, UCHL1, UCHL5, ubiquitinated proteins, and proteasome activity were elevated in the diabetic rats indicating activated UPS. Altered expression of ER-associated degradation (ERAD) components and increased ER stress markers were detected in 4-months diabetic rats. Proteasome inhibition by MG132 alleviated alterations in the UPS and ER stress in diabetic rat muscle. Conclusion Increased UPS activity and ER stress were implicated in the muscle atrophy of diabetic rats and proteasome inhibition exhibited beneficiary outcome.

      PubDate: 2017-12-27T00:56:20Z
      DOI: 10.1016/j.abb.2017.12.015
       
  • Improved rate of substrate oxidation catalyzed by genetically-engineered
           myoglobin
    • Authors: Subhash Chand; Sriparna Ray; Eranda Wanigasekara; Poonam Yadav; Joshua A. Crawford; Daniel W. Armstrong; Krishnan Rajeshwar; Brad S. Pierce
      Abstract: Publication date: Available online 23 December 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Subhash Chand, Sriparna Ray, Eranda Wanigasekara, Poonam Yadav, Joshua A. Crawford, Daniel W. Armstrong, Krishnan Rajeshwar, Brad S. Pierce
      This study showcases the potential of unnatural amino acids to enable non-natural functions when incorporated in the protein scaffold of heme metalloproteins. For this purpose, a genetically-engineered myoglobin (Mb) mutant was created by incorporating redox-active 3-amino-l-tyrosine (NH2Tyr) into its active site, replacing the distal histidine (H64) with NH2Tyr. In peroxide-shunt assays, this variant exhibits an increased rate of turnover for thioanisole and benzaldehyde oxidation as compared to the wild-type (WT) Mb. Indeed, in the presence of excess hydrogen peroxide (H2O2), a 9-fold and 81-fold increase in activity was observed over multiple turnovers for thioanisole sulfoxidation and benzoic acid formation, respectively. The increased oxidation activity in the H64NH2Tyr Mb mutant underlined the role of NH2Tyr in the distal active-site scaffold in peroxide activation. Kinetic, electrochemical, and EPR spectroscopic experiments are performed. On the basis of these studies, it is argued the single NH2Tyr residue within the Mb variant simultaneously serves the role of the conserved His/Arg-pair within the distal pocket of horseradish peroxidase.
      Graphical abstract image

      PubDate: 2017-12-24T00:38:03Z
      DOI: 10.1016/j.abb.2017.12.014
       
  • Membrane-damaging activities of mannosylated ovalbumin are involved in its
           antibacterial action
    • Authors: Yi-Jun Shi; Ren-Tsung Wang; Yu-Hui Chu; Ying-Jung Chen; Ching-Chia Tang; Yaw-Syan Fu; Yuan-Chin Lee; Liang-Jun Wang; Chia-Hui Huang; Long-Sen Chang
      Abstract: Publication date: Available online 19 December 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yi-Jun Shi, Ren-Tsung Wang, Yu-Hui Chu, Ying-Jung Chen, Ching-Chia Tang, Yaw-Syan Fu, Yuan-Chin Lee, Liang-Jun Wang, Chia-Hui Huang, Long-Sen Chang
      Mannosylated ovalbumin (Man-OVA) prepared by modification of carboxyl groups with p-aminophenyl α-d-mannopyranoside shows an increase of net positive charge, which may enhance its binding to bacterial membrane. Thus, we aimed to investigate whether Man-OVA exerts antibacterial activity on Escherichia coli and Staphylococcus aureus via membrane-perturbing effect. Man-OVA inhibited the growth of E. coli and S. aureus, whereas ovalbumin (OVA) did not show any antibacterial activity. Moreover, Man-OVA induced an increase in the membrane permeability of E. coli and S. aureus, which was positively correlated to its bactericidal action. Morphological examination using scanning electron microscopy revealed that Man-OVA disrupted the bacterial membrane integrity. Destabilization of the lipopolysaccharide (LPS) layer and inhibition of lipoteichoic acid (LTA) biosynthesis in the cell wall increased the bactericidal effect of Man-OVA. In contrast to OVA, Man-OVA also induced leakage of bacterial membrane-mimicking liposomes. Color transformation of phospholipid/polydiacetylene membrane assay revealed that the membrane-interaction mode of Man-OVA was distinct from that of OVA. LPS and LTA suppressed the membrane-damaging activity of Man-OVA, whereas an increase in the Man-OVA concentration attenuated the inhibitory action of LPS and LTA. Taken together, our data indicate that the bactericidal activity of Man-OVA depends strongly on its ability to induce membrane permeability.

      PubDate: 2017-12-24T00:38:03Z
      DOI: 10.1016/j.abb.2017.12.006
       
  • The alpha helix 1 from the first conserved region of HIV1 gp120 is
           reconstructed in the short NQ21 peptide
    • Authors: Vladislav Victorovich Khrustalev; Tatyana Aleksandrovna Khrustaleva; Ekaterina Yurievna Kahanouskaya; Yulia Anatolyevna Rudnichenko; Hanna Vitalyevna Bandarenka; Alexander Migranovich Arutyunyan; Kseniya Victorovna Girel; Nadia Vladimirovna Khinevich; Alexander Leonidovich Ksenofontov; Larisa Valentinovna Kordyukova
      Abstract: Publication date: Available online 19 December 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Vladislav Victorovich Khrustalev, Tatyana Aleksandrovna Khrustaleva, Ekaterina Yurievna Kahanouskaya, Yulia Anatolyevna Rudnichenko, Hanna Vitalyevna Bandarenka, Alexander Migranovich Arutyunyan, Kseniya Victorovna Girel, Nadia Vladimirovna Khinevich, Alexander Leonidovich Ksenofontov, Larisa Valentinovna Kordyukova
      Investigations of short peptides that can be used in the next phase of synthetic HIV1 vaccine development are an urgent goal, as well as investigations of peptides that can be used in immunological tests with the aim to check the titer of antibodies against the alpha helix 1 from the first conserved region of HIV1 gp120 that are known to cause antibody-dependent cellular cytotoxicity (ADCC). The aim of this work was to study the structure of the NQ21 peptide corresponding to the less mutable part of the first conserved region of HIV1 gp120 (residues 94–114). The NQ21 peptide and its conjugate with biotin (biotin-NQ21) are absolutely alpha-helical in phosphate buffer solutions at pH = 6.8, 7.4 and 8.0, as well as in the dried form, according to the results of surface-enhanced Raman scattering (SERS) spectroscopy. Results of the native gel electrophoresis and thermal analysis under the control of spectrofluorometer and near UV circular dichroism (CD) showed that the peptide exists in form of octamers and tetramers at pH = 7.4, that is important information for further vaccine development. Strong signal of interacting Trp residues in oligomers in the far UV CD obscures the signal from secondary structure, but becomes less intensive during the heating.

      PubDate: 2017-12-24T00:38:03Z
      DOI: 10.1016/j.abb.2017.12.004
       
  • Trichostatin A inhibits deacetylation of histone H3 and p53 by SIRT6
    • Authors: Marci Wood; Stacia Rymarchyk Song Zheng Yana Cen
      Abstract: Publication date: Available online 9 December 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Marci Wood, Stacia Rymarchyk, Song Zheng, Yana Cen
      SIRT6 is an epigenetic modification enzyme that regulates gene transcription through its deacetylase activity. In addition to histone protein, SIRT6 also modify other proteins and enzymes, some of which are central players in metabolic reprogramming and aging process. Therefore, SIRT6 has emerged as a therapeutic target for the treatment of metabolic disorder and age-related diseases. Here, we report that SIRT6 deacetylates lysine 382 of p53 in short synthetic peptide sequence and in full length p53. Further studies showed that the deacetylation of H3K9Ac and p53K382Ac are insensitive to nicotinamide inhibition, but are sensitive to trichostatin A (TSA) inhibition. Detailed kinetic analysis revealed that TSA competes with the peptide substrate for inhibition, and this inhibition is unique to SIRT6 in the sirtuin family. Taken together, this study not only suggests potential roles of SIRT6 in regulating apoptosis and stress resistance via direct deacetylation of p53, but also provides lead compound for the development of potent and selective SIRT6 inhibitors.

      PubDate: 2017-12-13T00:01:13Z
       
  • Mutational analysis and dynamic simulation of S-limonene synthase reveal
           the importance of Y573: Insight into the cyclization mechanism in
           monoterpene synthases
    • Authors: Jinkun Xu; Jingwei Xu; Ying Ai; Roba A. Farid; Li Tong; Dong Yang
      Abstract: Publication date: Available online 8 December 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Jinkun Xu, Jingwei Xu, Ying Ai, Roba A. Farid, Li Tong, Dong Yang
      Monoterpene synthases carry out complex reactions to produce multiple products from a sole substrate, geranyl pyrophosphate (GPP). S-limonene synthase (LS) is a model monoterpene synthase that can be explored to understand the catalytic mechanism of these enzymes. In this study, we have identified an active site tyrosine residue (Y573) is crucial for the enzyme activity and mutational analysis indicates that both the aromatic ring and hydroxyl group are essential for the catalysis. Dynamic simulations found a hydrogen bond between Y573 and D496 and also a significant conformational change in the helical form of the LPP intermediate. Further mutagenesis suggested that this hydrogen bond is essential for catalysis. Sequence analysis suggested Y573 is completely conserved among cyclic monoterpene synthases but variable in acyclic enzymes, indicating this residue may be involved in cyclization. Subsequent studies by using neryl diphosphate (NPP) as the substrate ruled out the possibility that Y573 functions solely at the substrate isomerization step. Therefore, a more complicated role may be played by this residue. We proposed that Y573 may be involved in the earlier steps of the reaction, probably by controlling the conformation of the helical LPP intermediate. Our study provides important insights not only on the catalytic mechanism of LS, but also on the cyclization of monoterpene synthases in general.

      PubDate: 2017-12-13T00:01:13Z
      DOI: 10.1016/j.abb.2017.12.007
       
  • Whole length myosin binding protein C stabilizes myosin S2 as measured by
           gravitational force spectroscopy
    • Authors: Rohit R. Singh; James W. Dunn; Motamed M. Qadan; Nakiuda Hall; Kathy K. Wang; Douglas D. Root
      Abstract: Publication date: Available online 8 December 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Rohit R. Singh, James W. Dunn, Motamed M. Qadan, Nakiuda Hall, Kathy K. Wang, Douglas D. Root
      The mechanical stability of the myosin subfragment-2 (S2) was tested with simulated force spectroscopy (SFS) and gravitational force spectroscopy (GFS). Experiments examined unzipping S2, since it required less force than stretching parallel to the coiled coil. Both GFS and SFS demonstrated that the force required to destabilize the light meromyosin (LMM) was greater than the force required to destabilize the coiled coil at each of three different locations along S2. GFS data also conveyed that the mechanical stability of the S2 region is independent from its association with the myosin thick filament using cofilaments of myosin tail and a single intact myosin. The C-terminal end of myosin binding protein C (MyBPC) binds to LMM and the N-terminal end can bind either S2 or actin. The force required to destabilize the myosin coiled coil molecule was 3 times greater in the presence of MyBPC than in its absence. Furthermore, the in vitro motility assay with full length slow skeletal MyBPC slowed down the actin filament sliding over myosin thick filaments. This study demonstrates that skeletal MyBPC both enhanced the mechanical stability of the S2 coiled coil and reduced the sliding velocity of actin filaments over polymerized myosin filaments.
      Graphical abstract image

      PubDate: 2017-12-13T00:01:13Z
      DOI: 10.1016/j.abb.2017.12.002
       
  • Characterizing interaction forces between actin and proteins of the
           tropomodulin family reveals the presence of the N-terminal actin-binding
           site in leiomodin
    • Authors: Baran Arslan; Mert Colpan; Kevin T. Gray; Nehal I. Abu-Lail; Alla S. Kostyukova
      Abstract: Publication date: Available online 6 December 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Baran Arslan, Mert Colpan, Kevin T. Gray, Nehal I. Abu-Lail, Alla S. Kostyukova
      Tropomodulin family of proteins includes several isoforms of tropomodulins (Tmod) and leiomodins (Lmod). These proteins can sequester actin monomers or nucleate actin polymerization. Although it is known that their actin-binding properties are isoform-dependent, knowledge on how they vary in strengths of interactions with G-actin is missing. While it is confirmed in many studies that Tmods have two actin-binding sites, information on number and location of actin-binding sites in Lmod2 is controversial. We used atomic force microscopy to study interactions between G-actin and proteins of the tropomodulin family. Unbinding forces between G-actin and Tmod1, Tmod2, Tmod3, or Lmod2 were quantified. Our results indicated that Tmod1 and Tmod3 had unimodal force distributions, Tmod2 had a bimodal distribution and Lmod2 had a trimodal distribution. The number of force distributions correlate with the proteins abilities to sequester actin or nucleate actin polymerization. We assigned specific unbinding forces to the individual actin-binding sites of Tmod2 and Lmod2 using mutations that destroy actin-binding sites of Tmod2 and truncated Lmod2. Our results confirm the existence of the N-terminal actin-binding site in Lmod2. Altogether, our data demonstrate how the differences between the number and the strength of actin-binding sites of Tmod or Lmod translate to their functional abilities.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/j.abb.2017.12.005
       
  • Understanding the molecular basis of the high oxygen affinity variant
           human hemoglobin Coimbra
    • Authors: S.E. Jorge; M. Bringas; A.A. Petruk; M. Arrar; M.A. Marti; M.S. Skaf; F.F. Costa; L. Capece; M.F. Sonati; D. Estrin
      Abstract: Publication date: Available online 1 December 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): S.E. Jorge, M. Bringas, A.A. Petruk, M. Arrar, M.A. Marti, M.S. Skaf, F.F. Costa, L. Capece, M.F. Sonati, D. Estrin
      Human hemoglobin (Hb) Coimbra (βAsp99Glu) is one of the seven βAsp99 Hb variants described to date. All βAsp99 substitutions result in increased affinity for O2 and decreased heme-heme cooperativity and their carriers are clinically characterized by erythrocytocis, caused by tissue hypoxia. Since βAsp99 plays an important role in the allosteric α1β2 interface and the mutation in Hb Coimbra only represents the insertion of a CH2 group in this interface, the present study of Hb Coimbra is important for a better understanding of the global impact of small modifications in this allosteric interface. We carried out functional, kinetic and dynamic characterization of this hemoglobin, focusing on the interpretation of these results in the context of a growth of the position 99 side chain length in the α1β2 interface. Oxygen affinity was evaluated by measuring p50 values in distinct pHs (Bohr effect), and the heme-heme cooperativity was analyzed by determining the Hill coefficient (n), in addition to the effect of the allosteric effectors inositol hexaphosphate (IHP) and 2,3-bisphosphoglyceric acid (2,3-BPG). Computer simulations revealed a stabilization of the R state in the Coimbra variant with respect to the wild type, and consistently, the T-to-R quaternary transition was observed on the nanosecond time scale of classical molecular dynamics simulations.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/j.abb.2017.11.010
       
  • Role of hydroxyl groups in the B-ring of flavonoids in stabilization of
           the Hoogsteen paired third strand of Poly(U).Poly(A)*Poly(U) triplex
    • Authors: Ankur Bikash Pradhan; Sutanwi Bhuiya; Lucy Haque; Suman Das
      Abstract: Publication date: Available online 21 November 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Ankur Bikash Pradhan, Sutanwi Bhuiya, Lucy Haque, Suman Das
      We have reported the interaction of two flavonoids namely quercetin (Q) and morin (M) with double stranded poly(A).poly(U) (herein after A.U) and triple stranded poly(U).poly(A)*poly(U) (herein after U.A*U, dot represents the Watson–Crick and asterisk represents Hoogsteen base pairing respectively) in this article. It has been observed that relative positions of hydroxyl groups on the B-ring of the flavonoids affect the stabilization of RNA. The double strand as well as the triple strand of RNA-polymers become more stabilized in presence of Q, however both the duplex and triplex remain unaffected in presence of M. The presence of catechol moiety on the B-ring of Q is supposed to be responsible for the stabilization. Moreover, after exploiting a series of biophysical experiments, it has been found that, triple helical RNA becomes more stabilized over its parent duplex in presence of Q. Fluorescence quenching, viscosity measurement and helix melting results establish the fact that Q binds with both forms of RNA through the mode of intercalation while M does not bind at all to either forms of RNA.
      Graphical abstract image

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/j.abb.2017.11.008
       
  • SNHG16/miR-216-5p/ZEB1 signal pathway contributes to the tumorigenesis of
           cervical cancer cells
    • Authors: Hong Zhu; Yan Zeng; Chen-chen Zhou; Weiping Ye
      Abstract: Publication date: Available online 7 November 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Hong Zhu, Yan Zeng, Chen-chen Zhou, Weiping Ye
      Long non-coding RNAs (lncRNAs) have been confirmed as crucial regulators in tumorgenesis. Small nucleolar RNA host gene 16 (SNHG16) has been recently uncovered to be a potential oncogene in several types of cancers. However, its expression level and potential role in cervical cancer remain uncertain. In our research, we assessed the expression level of SNHG16 in clinical cervical cancer tissues and cells. We made use of functional assays to determine the biological effects of SNHG16 on cell proliferation and migration of cervical cancer. By employing the bioinformatics analysis tools, we revealed that miR-216-5p could interact with SNHG16 and there existed a negative correlation between the expression levels of miR-216-5p and SNHG16 in cervical cancer specimens. Furthermore, RIP assay, RNA pulldown system and dual luciferase reporter assays confirmed that SNHG16 directly targeted miR-216-5p by harboring the binding sites of microRNA in the SNHG16 sequence. Additionally, bioinformatics analysis provided an evidence that ZEB1 was a potential target of miR-216-5p. Collectively, it was suggested that SNHG16 could serve as an oncogene that promoted tumor progression by acting as an endogenous ‘sponge’ to regulate miR-216A-5p/ZEB1.

      PubDate: 2017-11-08T15:55:15Z
      DOI: 10.1016/j.abb.2017.11.003
       
  • JNK signaling pathway regulates sorbitol-induced Tau proteolysis and
           apoptosis in SH-SY5Y cells by targeting caspase-3
    • Authors: Marta Olivera Santa-Catalina; Montaña Caballero Bermejo; Ricardo Argent; Juan C. Alonso; Francisco Centeno; María J. Lorenzo
      Abstract: Publication date: Available online 7 November 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Marta Olivera Santa-Catalina, Montaña Caballero Bermejo, Ricardo Argent, Juan C. Alonso, Francisco Centeno, María J. Lorenzo
      Growing evidence suggests that Diabetes Mellitus increases the risk of developing Alzheimer's disease. It is well known that hyperglycemia, a key feature of Diabetes Mellitus, may induce plasma osmolarity disturbances. Both hyperglycemia and hyperosmolarity promote the altered post-translational regulation of microtubule-associated protein Tau. Interestingly, abnormal hyperphosphorylation and cleavage of Tau have been proven to lead to the genesis of filamentous structures referred to as neurofibrillary tangles, the main pathological hallmark of Alzheimer's disease. We have previously described that hyperosmotic stress induced by sorbitol promotes Tau proteolysis and apoptosis in SH-SY5Y cells via caspase-3 activation. In order to gain insights into the regulatory mechanisms of such processes, in this work we explored the intracellular signaling pathways that regulate these events. We found that sorbitol treatment significantly enhanced the activation of conventional families of MAPK in SH-SY5Y cells. Tau proteolysis was completely prevented by JNK inhibition but not affected by either ERK1/2 or p38 MAPK blockade. Moreover, inhibition of JNK, but not ERK1/2 or p38 MAPK, efficiently prevented sorbitol-induced apoptosis and caspase-3 activation. In summary, we provide evidence that JNK signaling pathway is an upstream regulator of hyperosmotic stress-induced Tau cleavage and apoptosis in SH-SY5Y through the control of caspase-3 activation.

      PubDate: 2017-11-08T15:55:15Z
      DOI: 10.1016/j.abb.2017.11.004
       
  • Physiological serum copper concentrations found in malignancies cause
           unfolding induced aggregation of human serum albumin in vitro
    • Authors: Asim Rizvi; Mohd Furkan; Imrana Naseem
      Abstract: Publication date: Available online 6 November 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Asim Rizvi, Mohd Furkan, Imrana Naseem
      Malignancies are characterized by several drastic metabolic changes, one of which is a progressive rise in the levels of serum copper. This rise in serum copper is documented across all malignancies and across malignancies in several species. This study aims to explore in vitro the effect of increased copper levels on the structure of the blood protein human serum albumin. Exposure of human serum albumin to physiologically relevant copper concentrations for 21 days resulted in structural modifications in the protein which were evident by changes in the intrinsic florescence. A loss of the predominantly alpha helical structure of human serum albumin was recorded along with a tendency to form protein aggregates. This aggregation was characterized by Thioflavin T and Congo Red assays. Rayleigh light scattering and turbidity assays confirmed aggregation. The aggregates were visually confirmed using transmission electron microscopy. This is the first report implicating increased copper levels as a cause of aggregation of blood proteins in malignancies. The physiological and biochemical implications of this phenomenon are discussed.

      PubDate: 2017-11-08T15:55:15Z
      DOI: 10.1016/j.abb.2017.11.001
       
  • Thermodynamics of cooperative binding of FAD to human NQO1: Implications
           to understanding cofactor-dependent function and stability of the
           flavoproteome
    • Authors: Rafael Clavería-Gimeno; Adrian Velazquez-Campoy; Angel Luis Pey
      Abstract: Publication date: Available online 31 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Rafael Clavería-Gimeno, Adrian Velazquez-Campoy, Angel Luis Pey
      The stability of human flavoproteins strongly depends on flavin levels, although the structural and energetic basis of this relationship is poorly understood. Here, we report an in-depth analysis on the thermodynamics of FAD binding to one of the most representative examples of such relationship, NAD(P)H:quinone oxidoreductase 1 (NQO1). NQO1 is a dimeric enzyme that tightly binds FAD, which triggers large structural changes upon binding. A common cancer-associated polymorphism (P187S) severely compromises FAD binding. We show that FAD binding is described well by a thermodynamic model explicitly incorporating binding cooperativity when applied to different sets of calorimetric analyses and NQO1 variants, thus providing insight on the effects in vitro and in cells of cancer-associated P187S, its suppressor mutation H80R and the role of NQO1 C-terminal domain to modulate binding cooperativity and energetics. Furthermore, we show that FAD binding to NQO1 is very sensitive to physiologically relevant environmental conditions, such as the presence of phosphate buffer and salts. Overall, our results contribute to understanding at the molecular level the link between NQO1 stability and fluctuations of FAD levels intracellularly, and supports the notion that FAD binding energetics and cooperativity are fundamentally linked with the dynamic nature of apo-NQO1 conformational ensemble.

      PubDate: 2017-11-02T08:27:27Z
      DOI: 10.1016/j.abb.2017.10.020
       
  • Sexual dimorphism in oxidant-induced adaptive homeostasis in multiple
           wild-type D. melanogaster strains
    • Authors: Laura C.D. Pomatto; Sarah Wong; John Tower; Kelvin J.A. Davies
      Abstract: Publication date: Available online 31 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Laura C.D. Pomatto, Sarah Wong, John Tower, Kelvin J.A. Davies
      Sexual dimorphism includes the physical and reproductive differences between the sexes, including differences that are conserved across species, ranging from the common fruit fly, Drosophila melanogaster, to humans. Sex-dependent variations in adaptive homeostasis, and adaptive stress responses may offer insight into the underlying mechanisms for male and female survival differences and into differences in chronic disease incidence and severity in humans. Earlier work showed sex-specific differences in adaptive responses to oxidative stressors in hybrid laboratory strains of D. melanogaster. The present study explored whether this phenomenon is also observed in wild-type D. melanogaster strains Oregon-R (Or-R) and Canton-S (Ca-S), as well as the common mutant reference strain w[1118], in order to better understand whether such findings are descriptive of D. melanogaster in general. Flies of each strain were pretreated with non-damaging, adaptive concentrations of hydrogen peroxide (H2O2) or of different redox cycling agents (paraquat, DMNQ, or menadione). Adaptive homeostasis, and changes in the expression of the proteasome and overall cellular proteasomal proteolytic capacity were assessed. Redox cycling agents exhibited a male-specific adaptive response, whereas H2O2 exposure provoked female-specific adaptation. These findings demonstrate that different oxidants can elicit sexually dimorphic adaptive homeostatic responses in multiple fly strains. These results (and those contained in a parallel study [1]) highlight the need to address sex as a biological variable in both fundamental science, clinical research, and toxicology.

      PubDate: 2017-11-02T08:27:27Z
      DOI: 10.1016/j.abb.2017.10.021
       
  • Ru/Fe bimetallic complexes: Synthesis, characterization, cytotoxicity and
           study of their interactions with DNA/HSA and human topoisomerase IB
    • Authors: Jessica E. Takarada; Adriana P.M. Guedes; Rodrigo S. Correa; Elisângela de P. Silveira-Lacerda; Silvia Castelli; Federico Iacovelli; Victor Marcelo Deflon; Alzir Azevedo Batista; Alessandro Desideri
      Abstract: Publication date: Available online 28 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Jessica E. Takarada, Adriana P.M. Guedes, Rodrigo S. Correa, Elisângela de P. Silveira-Lacerda, Silvia Castelli, Federico Iacovelli, Victor Marcelo Deflon, Alzir Azevedo Batista, Alessandro Desideri
      Three ruthenium/iron-based compounds, 1: [Ru(MIm)(bipy)(dppf)]PF6 (MIm = 2-mercapto-1-methylimidazole anion), 2: [RuCl(Im)(bipy)(dppf)]PF6 (Im = imidazole), and 3: [Ru(tzdt)(bipy)(dppf)]PF6 (tzdt = 1,3-thiazolidine-2-thione anion) (dppf = 1,1′-bis(diphenylphosphine)ferrocene and bipy = 2,2′-bipyridine), were synthesized, and characterized by elemental analyses, conductivity, UV/Vis, IR, 1H, 13C and 31P{1H} NMR spectroscopies, and by electrochemical technique. The complex 3 was also characterized by single-crystal X-ray. The three ruthenium(II) complexes show cytotoxicity against DU-145 (prostate carcinoma cells) and A549 (lung carcinoma cells) tumor cells. The free ligands do not exhibit any cytotoxic activity, such as evident by the IC50 values higher than 200 μM. UV/Vis and viscosity experiments showed that the complexes interact weakly with the DNA molecule, via electrostatic forces. The interaction of the complexes 1–3 with the HSA is moderate, with Kb values in range of 105-107 M−1, presenting a static mechanism of interaction stabilized by hydrophobic. Complexes 2 and 3 showed high affinity for the FA7 HSA site as evidenced by fluorescence spectroscopy and molecular docking. Complexes 1–3 were tested as potential human Topoisomerase IB inhibitors by analysing the different steps of the enzyme catalytic cycle. The results indicate that all compounds efficiently inhibit the DNA relaxation and the cleavage reaction, in which the effect increases upon pre-incubation. Complexes 1 and 2 are also able to slow down the religation reaction.

      PubDate: 2017-11-02T08:27:27Z
      DOI: 10.1016/j.abb.2017.10.015
       
  • Kinetic and structural characterization of a cis-3-Chloroacrylic acid
           dehalogenase homologue in Pseudomonas sp. UW4: A potential step between
           subgroups in the tautomerase superfamily
    • Authors: Jake A. LeVieux; Bert-Jan Baas; Tamer S. Kaoud; Rebecca Davidson; Patricia C. Babbitt; Yan Jessie Zhang; Christian P. Whitman
      Abstract: Publication date: Available online 27 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Jake A. LeVieux, Bert-Jan Baas, Tamer S. Kaoud, Rebecca Davidson, Patricia C. Babbitt, Yan Jessie Zhang, Christian P. Whitman
      A Pseudomonas sp. UW4_01740 (designated Ps01740) protein of unknown function was identified as similar to 4-oxalocrotonate tautomerase (4-OT)-like and cis-3-chloroacrylic acid dehalogenase (cis-CaaD)-like subgroups of the tautomerase superfamily (TSF). Ps01740 lacks only Tyr-103 of the amino acids critical for cis-CaaD activity (Pro-1, His-28, Arg-70, Arg-73, Tyr-103, Glu-114). As Ps01740 may represent an important variant of these enzymes, its kinetic and structural properties have been determined. Ps01740 shows tautomerase activity with phenylenolpyruvate, but lacks native 4-OT activity and dehalogenase activity with the isomers of 3-chloroacrylic acid. Ps01740 shows mostly low-level hydratase activity at pH 7.0, converting 2-oxo-3-pentynoate to acetopyruvate, consistent with cis-CaaD-like behavior. At pH 9.0, this compound results primarily in covalent modification of Pro-1, which is consistent with 4-OT-like behavior. These observations could reflect a pK a for Pro-1 that is closer to that of cis-CaaD (∼9.2) than to 4-OT (∼6.4. A structure of the native enzyme, at 2.6 Å resolution, highlights differences at the active site from those of 4-OT and cis-CaaD that add to our understanding of how contemporary TSF reactions and mechanisms may have diverged from a common 4-OT-like ancestor.
      Graphical abstract image

      PubDate: 2017-11-02T08:27:27Z
      DOI: 10.1016/j.abb.2017.10.018
       
 
 
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