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  Subjects -> BIOLOGY (Total: 2985 journals)
    - BIOCHEMISTRY (232 journals)
    - BIOENGINEERING (105 journals)
    - BIOLOGY (1422 journals)
    - BIOPHYSICS (46 journals)
    - BIOTECHNOLOGY (216 journals)
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    - ENTOMOLOGY (63 journals)
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    - ORNITHOLOGY (25 journals)
    - PHYSIOLOGY (70 journals)
    - ZOOLOGY (134 journals)

BIOCHEMISTRY (232 journals)                  1 2 | Last

Showing 1 - 200 of 232 Journals sorted alphabetically
AAPS PharmSciTech     Hybrid Journal   (Followers: 6)
Acetic Acid Bacteria     Open Access   (Followers: 2)
ACS Central Science     Open Access   (Followers: 6)
ACS Chemical Biology     Full-text available via subscription   (Followers: 238)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 17)
Acta Crystallographica Section D : Biological Crystallography     Hybrid Journal   (Followers: 8)
Acta Crystallographica Section F: Structural Biology Communications     Hybrid Journal   (Followers: 7)
Advances and Applications in Bioinformatics and Chemistry     Open Access   (Followers: 9)
Advances in Biological Chemistry     Open Access   (Followers: 7)
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: 8)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 19)
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: 8)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 66)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 14)
American Journal of Polymer Science     Open Access   (Followers: 25)
Amino Acids     Hybrid Journal   (Followers: 7)
Analytical Biochemistry     Hybrid Journal   (Followers: 160)
Angiogenesis     Hybrid Journal   (Followers: 3)
Annals of Clinical Biochemistry     Hybrid Journal   (Followers: 7)
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: 44)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 17)
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)
Avicenna Journal of Medical Biochemistry     Open Access  
Bangladesh Journal of Medical Biochemistry     Open Access   (Followers: 2)
BBA Clinical     Open Access  
BBR : Biochemistry and Biotechnology Reports     Open Access   (Followers: 4)
Biocatalysis     Open Access  
Biochemical and Biophysical Research Communications     Hybrid Journal   (Followers: 21)
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: 25)
Biochemical Pharmacology     Hybrid Journal   (Followers: 9)
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: 284)
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: 8)
Biochimie     Hybrid Journal   (Followers: 7)
Biochimie Open     Open Access  
Bioconjugate Chemistry     Full-text available via subscription   (Followers: 29)
BioDrugs     Full-text available via subscription   (Followers: 7)
Bioelectrochemistry     Hybrid Journal   (Followers: 2)
Biofuels     Hybrid Journal   (Followers: 10)
Biogeochemistry     Hybrid Journal   (Followers: 13)
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: 24)
Biosimilars     Open Access   (Followers: 1)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 45)
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: 6)
Cellular Physiology and Biochemistry     Open Access   (Followers: 3)
ChemBioChem     Hybrid Journal   (Followers: 6)
Chemical and Biological Technologies for Agriculture     Open Access  
Chemical Biology & Drug Design     Hybrid Journal   (Followers: 20)
Chemical Engineering Journal     Hybrid Journal   (Followers: 34)
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: 6)
Chemistry & Biology     Full-text available via subscription   (Followers: 30)
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: 67)
Clinical Chemistry and Laboratory Medicine     Hybrid Journal   (Followers: 59)
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: 2)
Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology     Hybrid Journal   (Followers: 8)
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics     Hybrid Journal   (Followers: 3)
Comprehensive Biochemistry     Full-text available via subscription   (Followers: 1)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 12)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 5)
Current Chemical Biology     Hybrid Journal   (Followers: 2)
Current Medicinal Chemistry     Hybrid Journal   (Followers: 15)
Current Opinion in Chemical Biology     Hybrid Journal   (Followers: 26)
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: 55)
FEBS Open Bio     Open Access   (Followers: 3)
Fish Physiology and Biochemistry     Hybrid Journal   (Followers: 4)
Food & Function     Full-text available via subscription   (Followers: 5)
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: 15)
Green Chemistry     Full-text available via subscription   (Followers: 9)
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: 8)
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   (Followers: 1)
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: 2)
Journal of Biochemistry     Hybrid Journal   (Followers: 43)
Journal of Biological Chemistry     Full-text available via subscription   (Followers: 190)
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: 1)
Journal of Chemical Neuroanatomy     Hybrid Journal  
Journal of Clinical Lipidology     Hybrid Journal   (Followers: 1)
Journal of Comparative Physiology B : Biochemical, Systemic, and Environmental Physiology     Hybrid Journal   (Followers: 4)
Journal of Drug Discovery and Therapeutics     Open Access  
Journal of Enzyme Inhibition and Medicinal Chemistry     Hybrid Journal   (Followers: 3)
Journal of Evolutionary Biochemistry and Physiology     Hybrid Journal  
Journal of Food and Drug Analysis     Open Access  
Journal of Forensic Toxicology and Pharmacology     Hybrid Journal   (Followers: 4)
Journal of Inborn Errors of Metabolism and Screening     Open Access  
Journal of Inorganic Biochemistry     Hybrid Journal   (Followers: 6)
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: 7)
Journal of Neurochemistry     Hybrid Journal   (Followers: 3)
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: 5)
Journal of Wood Chemistry and Technology     Hybrid Journal   (Followers: 7)
La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine     Hybrid Journal  
Lab on a Chip     Full-text available via subscription   (Followers: 34)
Marine Chemistry     Hybrid Journal   (Followers: 6)
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: 2)
Molecular Informatics     Hybrid Journal   (Followers: 6)
Molecular inhibitors in targeted therapy     Open Access  
Moscow University Chemistry Bulletin     Hybrid Journal   (Followers: 1)
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: 71)
Nature Communications     Open Access   (Followers: 174)
Neurosignals     Open Access  
NOVA     Open Access  
Novelty in Biomedicine     Open Access  
OA Biochemistry     Open Access   (Followers: 1)
OA Inflammation     Open Access  
Ocean Acidification     Open Access   (Followers: 3)
Organic & Biomolecular Chemistry     Full-text available via subscription   (Followers: 89)
Peptidomics     Open Access  
Pesticide Biochemistry and Physiology     Hybrid Journal   (Followers: 4)
Pflugers Archiv European Journal of Physiology     Hybrid Journal   (Followers: 3)

        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  [3042 journals]
  • PKM2-mediated inhibition of autophagy facilitates Tat's inducing HIV-1
           transactivation
    • Authors: Hong-Sheng Zhang; Zhong-Guo Zhang; Zhen Zhou; Guang-Yuan Du; Hu Li; Xiao-Ying Yu; Ying-Hui Huang
      Pages: 17 - 23
      Abstract: Publication date: Available online 2 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Hong-Sheng Zhang, Zhong-Guo Zhang, Zhen Zhou, Guang-Yuan Du, Hu Li, Xiao-Ying Yu, Ying-Hui Huang
      Considerable evidence has shown that autophagy has an important role in HIV-1 infection. However, it is still unknown whether metabolism-regulated autophagy pathway is involved in Tat-mediated HIV-1 transactivation. This study demonstrated that treatment of Tat in TZM-bl cells significantly down-regulated protein levels of Beclin-1, Atg-5, Atg-7, and LC3B-II and up-regulated of p62 levels. Blockage of autophagy enhanced Tat-induced HIV-1 transactivation in TZM-bl cells. Moreover, we found that Tat activated the Akt/mTOR and inhibited AMPK signaling pathway that was related to its up-regulation of PKM2 expression. In addition, we showed that PI3K/AKT activation and AMPK inhibtion was required for the PKM2-mediated inhibition of autophagy in Tat-treated TZM-bl cells. In conclusion, our data reveals that PKM2-mediated autophagy inhibition is required for Tat-mediated HIV-1 transactivation. Metabolism-related autophagic pathway may act as a promising diagnostic and therapeutic tool for HIV-1 infection in the future.

      PubDate: 2017-06-07T07:30:27Z
      DOI: 10.1016/j.abb.2017.05.018
      Issue No: Vol. 625-626 (2017)
       
  • The lncRNA UCA1 interacts with miR-182 to modulate glioma proliferation
           and migration by targeting iASPP
    • Authors: Zongze He; Yujue Wang; Guangfu Huang; Qi Wang; Dongdong Zhao; Longyi Chen
      Pages: 1 - 8
      Abstract: Publication date: 1 June 2017
      Source:Archives of Biochemistry and Biophysics, Volumes 623–624
      Author(s): Zongze He, Yujue Wang, Guangfu Huang, Qi Wang, Dongdong Zhao, Longyi Chen
      Long non-coding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) has been reported to be involved in the development and progression of many types of tumors including breast cancer, gastric cancer, and bladder cancer. However, the exact effects and molecular mechanisms of UCA1 in glioma progression remain unclear up to now. In this study, we firstly found that UCA1 was upregulated in glioma tumor samples and negatively correlated with survival time. Then, we investigated the role of UCA1 in human glioma cell lines. Our results showed that upregulation of lncRNA-UCA1 in glioma tissues and cell lines could promote glioma cell proliferation and migration through interaction with miR-182, and knockdown of UCA1 inhibited the proliferation and migration of human glioma cell. In addition, miR-182 dependent inhibitor of apoptosis-stimulating protein of p53 (iASPP) was required in the regulation of UCA1 induced glioma cell proliferation. Taken together, UCA1 might promote proliferation and migration of glioma, to regulate the tumor growth and metastasis via miR-182 dependent iASPP regulation. Therefore, lncRNA-UCA1 could be regarded as a therapeutic target in human glioma.

      PubDate: 2017-05-23T04:54:15Z
      DOI: 10.1016/j.abb.2017.01.013
      Issue No: Vol. 623-624 (2017)
       
  • Antimicrobial mechanism of epigallocatechin gallate and gallocatechin
           gallate: They target 1-deoxy-d-xylulose 5-phosphate reductoisomerase, the
           key enzyme of the MEP terpenoid biosynthetic pathway
    • Authors: Xian Hui; Shui-Hong Hua; Qian-Qian Wu; Heng Li; Wen-Yun Gao
      Pages: 1 - 8
      Abstract: Publication date: 15 May 2017
      Source:Archives of Biochemistry and Biophysics, Volume 622
      Author(s): Xian Hui, Shui-Hong Hua, Qian-Qian Wu, Heng Li, Wen-Yun Gao
      The catechins EGCG and GCG show a variety of pharmacological activities, especially an antibacterial capacity, but their modes of antimicrobial action have not been fully elucidated. 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), the first key enzyme in the MEP pathway for terpenoid biosynthesis, is a recently validated antimicrobial target. In order to disclose the antibacterial mechanism of EGCG and GCG, the DXR inhibitory activity of them was investigated in this study. The data show that EGCG and GCG both could specifically suppress the activity of DXR, with EGCG exhibiting relatively low effect against DXR (IC50 about 210 μM) and GCG displaying strong activity (IC50 27.5 μM). In addition, studies on inhibition kinetics of the catechins against DXR demonstrate that they are competitive inhibitors of DXR against DXP and uncompetitive inhibitors with respect to NADPH. Meanwhile, the possible interactions between DXR and the catechine, esyth onlols were simulated via docking experiments.
      Graphical abstract image

      PubDate: 2017-04-25T03:08:37Z
      DOI: 10.1016/j.abb.2017.04.007
      Issue No: Vol. 622 (2017)
       
  • Tyrosine oxidation and nitration in transmembrane peptides is connected to
           lipid peroxidation
    • Authors: Silvina Bartesaghi; Daniel Herrera; Débora M. Martinez; Ariel Petruk; Verónica Demicheli; Madia Trujillo; Marcelo A. Martí; Darío A. Estrín; Rafael Radi
      Pages: 9 - 25
      Abstract: Publication date: Available online 13 April 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Silvina Bartesaghminni, Daniel Herrera, Débora M. Martinez, Ariel Petruk, Verónica Demicheli, Madia Trujillo, Marcelo A. Martí, Darío A. Estrín, Rafael Radi
      Tyrosine nitration is an oxidative post-translational modification that can occur in proteins associated to hydrophobic bio-structures such as membranes and lipoproteins. In this work, we have studied tyrosine nitration in membranes using a model system consisting of phosphatidylcholine liposomes with pre-incorporated tyrosine-containing 23 amino acid transmembrane peptides. Tyrosine residues were located at positions 4, 8 or 12 of the amino terminal, resulting in different depths in the bilayer. Tyrosine nitration was accomplished by exposure to peroxynitrite and a peroxyl radical donor or hemin in the presence of nitrite. In egg yolk phosphatidylcholine liposomes, nitration was highest for the peptide with tyrosine at position 8 and dramatically increased as a function of oxygen levels. Molecular dynamics studies support that the proximity of the tyrosine phenolic ring to the linoleic acid peroxyl radicals contributes to the efficiency of tyrosine oxidation. In turn, α-tocopherol inhibited both lipid peroxidation and tyrosine nitration. The mechanism of tyrosine nitration involves a “connecting reaction” by which lipid peroxyl radicals oxidize tyrosine to tyrosyl radical and was fully recapitulated by computer-assisted kinetic simulations. Altogether, this work underscores unique characteristics of the tyrosine oxidation and nitration process in lipid-rich milieu that is fueled via the lipid peroxidation process.
      Graphical abstract image

      PubDate: 2017-04-25T03:08:37Z
      DOI: 10.1016/j.abb.2017.04.006
      Issue No: Vol. 622 (2017)
       
  • Hyperthermophilic L-asparaginase bypasses monomeric intermediates during
           folding to retain cooperativity and avoid amyloid assembly
    • Authors: Dushyant K. Garg; Bishwajit Kundu
      Pages: 36 - 46
      Abstract: Publication date: Available online 28 April 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Dushyant K. Garg, Bishwajit Kundu
      In obligate dimeric proteins of hyperthermophilic origin the question whether the native dimer is obtained by association of folded monomers or through concomitant folding and assembly of subunits has intrigued researchers. To find an answer we studied the folding of a dimeric enzyme L-asparaginase from Pyrococcus furiosus (PfA) for which we reported earlier that it unfolds cooperatively without populating folded monomeric intermediates. However, in the present study we report the finding of a folded monomeric intermediate of PfA under acidic condition. This monomer, although inactive, displayed secondary and tertiary structural features identical to the native protein and re-assembled to active dimeric form upon reversal of pH. The monomer is conformationally flexible and thermodynamically and kinetically less stable than the native dimer. Interestingly, when incubated at 60 °C the folded monomer, with exposed ANS-binding hydrophobic surfaces, spontaneously converted to amyloid fibrils. On the basis of our data we propose that PfA directly assembles into a multimeric form perhaps as an evolutionary adaptation to avoid accumulation of aggregation prone monomeric intermediates.

      PubDate: 2017-05-02T03:35:08Z
      DOI: 10.1016/j.abb.2017.04.010
      Issue No: Vol. 622 (2017)
       
  • MsrB3 deficiency induces cancer cell apoptosis through p53-independent and
           ER stress-dependent pathways
    • Authors: Geun-Hee Kwak; Hwa-Young Kim
      Pages: 1 - 5
      Abstract: Publication date: 1 May 2017
      Source:Archives of Biochemistry and Biophysics, Volume 621
      Author(s): Geun-Hee Kwak, Hwa-Young Kim
      We have previously shown that down-regulation of methionine sulfoxide reductase B3 (MsrB3) induces cancer cell apoptosis through the activation of the intrinsic mitochondrial pathway. However, the mechanism through which MsrB3 deficiency results in cancer cell death is poorly understood. In this study, we investigated whether p53 and endoplasmic reticulum (ER) stress are involved in MsrB3 deficiency-induced cancer cell apoptosis using breast and colon cancer cells. MsrB3 depletion resulted in p53 down-regulation at the post-transcriptional level. MsrB3 deficiency induced cell death to a similar extent in both p53 wild-type (p53 +/+) and null (p53 −/−) cancer cells, suggesting that MsrB3 deficiency-induced apoptosis occurs independently of p53. MsrB3 deficiency significantly increased ER stress, which resulted in apoptosis. In addition, MsrB3 depletion activated the pro-apoptotic Bim molecule, which is essential for ER stress-induced apoptosis. MsrB3 deficiency increased cytosolic calcium levels, suggesting that MsrB3 down-regulation leads to a disturbance of calcium homeostasis in the ER, which consequently triggers ER stress. MsrB3 overexpression in MsrB3-depleted cells reduced ER stress, and was accompanied by at least partial recovery of cell viability. Taken together, our results suggest that MsrB3 plays a critical role in cancer cell apoptosis through the modulation of ER stress status.

      PubDate: 2017-04-25T03:08:37Z
      DOI: 10.1016/j.abb.2017.04.001
      Issue No: Vol. 621 (2017)
       
  • Structural insights into the activation mechanisms of human HtrA serine
           proteases
    • Authors: Dorota Zurawa-Janicka; Tomasz Wenta; Miroslaw Jarzab; Joanna Skorko-Glonek; Przemyslaw Glaza; Artur Gieldon; Jerzy Ciarkowski; Barbara Lipinska
      Pages: 6 - 23
      Abstract: Publication date: 1 May 2017
      Source:Archives of Biochemistry and Biophysics, Volume 621
      Author(s): Dorota Zurawa-Janicka, Tomasz Wenta, Miroslaw Jarzab, Joanna Skorko-Glonek, Przemyslaw Glaza, Artur Gieldon, Jerzy Ciarkowski, Barbara Lipinska
      Human HtrA1-4 proteins belong to the HtrA family of evolutionarily conserved serine proteases and function as important modulators of many physiological processes, including maintenance of mitochondrial homeostasis, cell signaling and apoptosis. Disturbances in their action are linked to severe diseases, including oncogenesis and neurodegeneration. The HtrA1-4 proteins share structural and functional features of other members of the HtrA protein family, however there are several significant differences in structural architecture and mechanisms of action which makes each of them unique. Our goal is to present recent studies regarding human HtrAs. We focus on their physiological functions, structure and regulation, and describe current models of activation mechanisms. Knowledge of molecular basis of the human HtrAs' action is a subject of great interest; it is crucial for understanding their relevance in cellular physiology and pathogenesis as well as for using them as targets in future therapies of diseases such as neurodegenerative disorders and cancer.

      PubDate: 2017-04-25T03:08:37Z
      DOI: 10.1016/j.abb.2017.04.004
      Issue No: Vol. 621 (2017)
       
  • N-acetylcysteine improves the quality of red blood cells stored for
           transfusion
    • Authors: Florencia Amen; Andrea Machin; Cristina Touriño; Ismael Rodríguez; Ana Denicola; Leonor Thomson
      Pages: 31 - 37
      Abstract: Publication date: 1 May 2017
      Source:Archives of Biochemistry and Biophysics, Volume 621
      Author(s): Florencia Amen, Andrea Machin, Cristina Touriño, Ismael Rodríguez, Ana Denicola, Leonor Thomson
      Storage inflicts a series of changes on red blood cells (RBC) that compromise the cell survival and functionality; largely these alterations (storage lesions) are due to oxidative modifications. The possibility of improving the quality of packed RBC stored for transfusion including N-acetylcysteine (NAC) in the preservation solution was explored. Relatively high concentrations of NAC (20–25 mM) were necessary to prevent the progressive leakage of hemoglobin, while lower concentrations (≥2.5 mM) were enough to prevent the loss of reduced glutathione during the first 21 days of storage. Peroxiredoxin-2 was also affected during storage, with a progressive accumulation of disulfide-linked dimers and hetero-protein complexes in the cytosol and also in the membrane of stored RBC. Although the presence of NAC in the storage solution was unable to avoid the formation of thiol-mediated protein complexes, it partially restored the capacity of the cell to metabolize H2O2, indicating the potential use of NAC as an additive in the preservation solution to improve RBC performance after transfusion.

      PubDate: 2017-04-25T03:08:37Z
      DOI: 10.1016/j.abb.2017.02.012
      Issue No: Vol. 621 (2017)
       
  • FBXO25 regulates MAPK signaling pathway through inhibition of ERK1/2
           phosphorylation
    • Authors: Felipe R. Teixeira; Adriana O. Manfiolli; Nichelle A. Vieira; Ana Carla Medeiros; Priscila de O. Coelho; Dimitrius Santiago Guimarães; Deborah Schechtman; Marcelo D. Gomes
      Pages: 38 - 45
      Abstract: Publication date: 1 May 2017
      Source:Archives of Biochemistry and Biophysics, Volume 621
      Author(s): Felipe R. Teixeira, Adriana O. Manfiolli, Nichelle A. Vieira, Ana Carla Medeiros, Priscila de O. Coelho, Dimitrius Santiago Guimarães, Deborah Schechtman, Marcelo D. Gomes
      The FBXO25 mediates degradation of ELK-1 and thus inhibits transcriptional activation of immediate early genes (iEG). Here we show that FBXO25 regulates yet another node of this signaling pathway, by decreasing MAPK/ERK activity. We show that induction of FBXO25 reduced ERK1/2 phosphorylation independently of MEK1/2. Accordingly, in HAP1 FBXO25 knockout cells (FBXO25KO), we observed that upon PMA treatment ERK1/2 was more active than in parental cells. An increase in cell proliferation under receptor mediated activation of the ERK signaling pathway in FBXO25KO cells was also observed. Taken together we show that FBXO25 functions as a negative regulator of MAPK signaling though the reduction of ERK1/2 activation.

      PubDate: 2017-04-25T03:08:37Z
      DOI: 10.1016/j.abb.2017.04.003
      Issue No: Vol. 621 (2017)
       
  • Ascorbic acid inhibits human insulin aggregation and protects against
           amyloid induced cytotoxicity
    • Authors: Parvez Alam; Ayesha Zainab Beg; Mohammad Khursheed Siddiqi; Sumit Kumar Chaturvedi; Ravi Kant Rajpoot; Mohd Rehan Ajmal; Masihuz Zaman; Ali S. Abdelhameed; Rizwan Hasan Khan
      Pages: 54 - 62
      Abstract: Publication date: 1 May 2017
      Source:Archives of Biochemistry and Biophysics, Volume 621
      Author(s): Parvez Alam, Ayesha Zainab Beg, Mohammad Khursheed Siddiqi, Sumit Kumar Chaturvedi, Ravi Kant Rajpoot, Mohd Rehan Ajmal, Masihuz Zaman, Ali S. Abdelhameed, Rizwan Hasan Khan
      Protein aggregation into oligomers and fibrils are associated with many human pathophysiologies. Compounds that modulate protein aggregation and interact with preformed fibrils and convert them to less toxic species, expect to serve as promising drug candidates and aid to the drug development efforts against aggregation diseases. In present study, the kinetics of amyloid fibril formation by human insulin (HI) and the anti-amyloidogenic activity of ascorbic acid (AA) were investigated by employing various spectroscopic, imaging and computational approaches. We demonstrate that ascorbic acid significantly inhibits the fibrillation of HI in a dose-dependent manner. Interestingly ascorbic acid destabilise the preformed amyloid fibrils and protects human neuroblastoma cell line (SH- SY5Y) against amyloid induced cytotoxicity. The present data signifies the role of ascorbic acid that can serve as potential molecule in preventing human insulin aggregation and associated pathophysiologies.

      PubDate: 2017-04-25T03:08:37Z
      DOI: 10.1016/j.abb.2017.04.005
      Issue No: Vol. 621 (2017)
       
  • Stimulatory and inhibitory effects of PKC isozymes are mediated by
           serine/threonine PKC sites of the Cav2.3α1 subunits
    • Authors: Ganesan L. Kamatchi; Senthilkumar Rajagopal; Brittney K. Burton
      First page: 399a
      Abstract: Publication date: 1 May 2017
      Source:Archives of Biochemistry and Biophysics, Volume 621
      Author(s): Senthilkumar Rajagopal, Brittney K. Burton, Blanche L. Fields, India O. El, Ganesan L. Kamatchi
      Protein kinase C (PKC) isozymes modulate voltage-gated calcium (Cav) currents through Cav2.2 and Cav2.3 channels by targeting serine/threonine (Ser/Thr) phosphorylation sites of Cavα1 subunits. Stimulatory (Thr-422, Ser-2108 and Ser-2132) and inhibitory (Ser-425) sites were identified in the Cav2.2α1 subunits to PKCs βII and ε. In the current study, we investigated if the homologous sites of Cav2.3α1 subunits (stimulatory: Thr-365, Ser-1995 and Ser-2011; inhibitory: Ser-369) behaved in similar manner. Several Ala and Asp mutants were constructed in Cav2.3α1 subunits in such a way that the Ser/Thr sites can be examined in isolation. These mutants or WT Cav2.3α1 along with auxiliary β1b and α2/δ subunits were expressed in Xenopus oocytes and the effects of PKCs βII and ε studied on the barium current (I Ba). Among these sites, stimulatory Thr-365 and Ser-1995 and inhibitory Ser-369 behaved similar to their homologs in Cav2.2α1 subunits. Furthermore PKCs produced neither stimulation nor inhibition when stimulatory Thr-365 or Ser-1995 and inhibitory Ser-369 were present together. However, the PKCs potentiated the I Ba when two stimulatory sites, Thr-365 and Ser-1995 were present together, thus overcoming the inhibitory effect of Ser-369. Taken together net PKC effect may be the difference between the responses of the stimulatory and inhibitory sites.

      PubDate: 2017-04-25T03:08:37Z
      DOI: 10.1016/j.bpj.2016.11.2166
      Issue No: Vol. 112, No. 3 (2017)
       
  • Advances in stable isotope assisted labeling strategies with information
           science
    • Authors: Takanori Kigawa
      Abstract: Publication date: Available online 20 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Takanori Kigawa
      Stable-isotope (SI) labeling of proteins is an essential technique to investigate their structures, interactions or dynamics by nuclear magnetic resonance (NMR) spectroscopy. The assignment of the main-chain signals, which is the fundamental first step in these analyses, is usually achieved by a sequential assignment method based on triple resonance experiments. Independently of the triple resonance experiment-based sequential assignment, amino acid-selective SI labeling is beneficial for discriminating the amino acid type of each signal; therefore, it is especially useful for the signal assignment of difficult targets. Various combinatorial selective labeling schemes have been developed as more sophisticated labeling strategies. In these strategies, amino acids are represented by combinations of SI labeled samples, rather than simply assigning one amino acid to one SI labeled sample as in the case of conventional amino acid-selective labeling. These strategies have proven to be useful for NMR analyses of difficult proteins, such as those in large complex systems, in living cells, attached or integrated into membranes, or with poor solubility. In this review, recent advances in stable isotope assisted labeling strategies will be discussed.

      PubDate: 2017-06-22T07:10:39Z
      DOI: 10.1016/j.abb.2017.06.014
       
  • Applications of NMR to structure determination of RNAs large and small
    • Authors: Ravi P. Barnwal; Fan Yang; Gabriele Varani
      Abstract: Publication date: Available online 6 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Ravi P. Barnwal, Fan Yang, Gabriele Varani
      Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool to investigate the structure and dynamics of RNA, because many biologically important RNAs have conformationally flexible structures, which makes them difficult to crystallize. Functional, independently folded RNA domains, range in size between simple stem-loops of as few as 10–20 nucleotides, to 50–70 nucleotides, the size of tRNA and many small ribozymes, to a few hundred nucleotides, the size of more complex RNA enzymes and of the functional domains of non-coding transcripts. In this review, we discuss new methods for sample preparation, assignment strategies and structure determination for independently folded RNA domains of up to 100 kDa in molecular weight.

      PubDate: 2017-06-22T07:10:39Z
      DOI: 10.1016/j.abb.2017.06.003
       
  • Flavin-dependent epitranscriptomic world
    • Authors: Murielle Lombard; Djemel Hamdane
      Abstract: Publication date: Available online 15 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Murielle Lombard, Djemel Hamdane
      RNAs molecules fulfill key roles in the expression and regulation of the genetic information stored within the DNA chromosomes. In addition to the four canonical bases, U, C, A and G, RNAs harbor various chemically modified derivatives which are generated post-transcriptionally by specific enzymes acting directly at the polymer level. More than one hundred naturally occurring modified nucleosides have been identified to date, the largest number of which is found in tRNAs and rRNA. This remarkable biochemical process produces widely diversified RNAs further expanding the functional repertoires of these nucleic acids. Interestingly, several RNA-modifying enzymes use a flavin bioorganic molecule as a coenzyme in RNA modification pathways. Some of these reactions are simple while others are extremely complex using challenging chemistry orchestrated by large flavoenzymatic systems. In this review, we summarize recent knowledges on the flavin-dependent RNA-modifying enzymes and discuss the relevance of their activity within a cellular context.

      PubDate: 2017-06-16T08:23:07Z
      DOI: 10.1016/j.abb.2017.06.011
       
  • Inhibitory effect of vitamin B3 against glycation and reactive oxygen
           species production in HSA: An in vitro approach
    • Authors: K.M. Abdullah; Faizan Abul Qais; Iqbal Ahmad; Imrana Naseem
      Abstract: Publication date: Available online 15 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): K.M. Abdullah, Faizan Abul Qais, Iqbal Ahmad, Imrana Naseem
      Hyperglycaemia is a key factor for the formation of advanced glycated endproducts (AGEs). Inhibition of glycation may play key role in minimizing the diabetes related complications. We have tried to explore the glucose and methyl glyoxal mediated glycation and antiglycation activity of niacin using human serum albumin as model protein. Protein was incubated with glucose for 28 days at physiological temperature to achieve glycation. Antiglycation activity was evaluated by assessing free lysine, carbonyl content, AGE specific fluorescence. Molecular docking and isothermal titration calorimetry was deployed to study the interaction of niacin with HSA and get a detailed insight of binding site and thermodynamics of interaction. Niacin reduced the glycation significantly which was evident from the estimation of free lysine and carbonyl content. Niacin binds with HSA in a spontaneous manner with the binding constant in the range of 104 M−1. Niacin also prevented the loss in secondary structure induced by glycation. Reactive oxygen species were also effectively quenched by niacin leading to protection from DNA damage. Niacin was found to be located at Sudlow's site I with binding energy of 5.3 kcal/mol. These results clearly highlight the antiglycation activity of niacin and its potential in preventing disease progression in diabetes.

      PubDate: 2017-06-16T08:23:07Z
      DOI: 10.1016/j.abb.2017.06.009
       
  • Amine oxidation by d-arginine dehydrogenase in Pseudomonas aeruginosa
    • Authors: Daniel Ouedraogo; Jacob Ball; Archana Iyer; Renata A.G. Reis; Maria Vodovoz; Giovanni Gadda
      Abstract: Publication date: Available online 15 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Daniel Ouedraogo, Jacob Ball, Archana Iyer, Renata A.G. Reis, Maria Vodovoz, Giovanni Gadda
      d-Arginine dehydrogenase from Pseudomonas aeruginosa (PaDADH) is a flavin-dependent oxidoreductase, which is part of a novel two-enzyme racemization system that functions to convert d-arginine to l-arginine. PaDADH contains a noncovalently linked FAD that shows the highest activity with d-arginine. The enzyme exhibits broad substrate specificity towards d-amino acids, particularly with cationic and hydrophobic d-amino acids. Biochemical studies have established the structure and the mechanistic properties of the enzyme. The enzyme is a true dehydrogenase because it displays no reactivity towards molecular oxygen. As established through solvent and multiple kinetic isotope studies, PaDADH catalyzes an asynchronous CH and NH bond cleavage via a hydride transfer mechanism. Steady-state kinetic studies with d-arginine and d-histidine are consistent with the enzyme following a ping-pong bi-bi mechanism. As shown by a combination of crystallography, kinetic and computational data, the shape and flexibility of loop L1 in the active site of PaDADH are important for substrate capture and broad substrate specificity.

      PubDate: 2017-06-16T08:23:07Z
      DOI: 10.1016/j.abb.2017.06.013
       
  • Pressure effects on α-synuclein amyloid fibrils: An experimental
           investigation on their dissociation and reversible nature
    • Authors: Federica Piccirilli; Nicoletta Plotegher; Francesco Spinozzi; Luigi Bubacco; Paolo Mariani; Mariano Beltramini; Isabella Tessari; Valeria Militello; Andrea Perucchi; Heinz Wilfried Amenitsch; Enrico Baldassarri; Milos Steinhart; Stefano Lupi; Maria Grazia Ortore
      Abstract: Publication date: Available online 15 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Federica Piccirilli, Nicoletta Plotegher, Francesco Spinozzi, Luigi Bubacco, Paolo Mariani, Mariano Beltramini, Isabella Tessari, Valeria Militello, Andrea Perucchi, Heinz Wilfried Amenitsch, Enrico Baldassarri, Milos Steinhart, Stefano Lupi, Maria Grazia Ortore
      α–synuclein amyloid fibrils are found in surviving neurons of Parkinson's disease affected patients, but the role they play in the disease development is still under debate. A growing number of evidences points to soluble oligomers as the major cytotoxic species, while insoluble fibrillar aggregates could even play a protection role. In this work, we investigate α–synuclein fibrils dissociation induced at high pressure by means of Small Angle X-ray Scattering and Fourier Transform Infrared Spectroscopy. Fibrils were produced from wild type α–synuclein and two familial mutants, A30P and A53T. Our results enlighten the different reversible nature of α–synuclein fibrils fragmentation at high pressure and suggest water excluded volumes presence in the fibrils core. Wild type and A30P species stabilized at high pressure are highly amyloidogenic and quickly re-associate into fibrils upon decompression, while A53T species shows a partial reversibility of the process likely due to the presence of an intermediate oligomeric state stabilized at high pressure. The amyloid fibrils dissociation process is here suggested to be associated to a negative activation volume, supporting the notion that α–synuclein fibrils are in a high-volume and high-compressibility state and hinting at the presence of a hydration-mediated activated state from which dissociation occurs.

      PubDate: 2017-06-16T08:23:07Z
      DOI: 10.1016/j.abb.2017.06.007
       
  • Genome-wide identification and expression profiling of EIL gene family in
           woody plant representative poplar (Populus trichocarpa)
    • Authors: Ertugrul Filiz; Recep Vatansever; Ibrahim Ilker Ozyigit; Mehmet Emin Uras; Ugur Sen; Naser A. Anjum; Eduarda Pereira
      Abstract: Publication date: Available online 15 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Ertugrul Filiz, Recep Vatansever, Ibrahim Ilker Ozyigit, Mehmet Emin Uras, Ugur Sen, Naser A. Anjum, Eduarda Pereira
      This study aimed to improve current understanding on ethylene-insensitive 3-like (EIL) members, least explored in woody plants such as poplar (Populus trichocarpa Torr. & Gray). Herein, seven putative EIL members were identified in P. trichocarpa genome and were roughly annotated either as EIN3-like sequence associated with ethylene pathway or EIL3-like sequences related with sulfur (S)-pathway. Motif-distribution pattern of proteins also corroborated this annotation. They were distributed on six chromosomes (chr1, 3, 4 and 8–10), and were revealed to encode a protein of 509–662 residues with nuclear localization. The presence of ethylene insensitive 3 (EIN3; PF04873) domain (covering first 80–280 residues from N-terminus) was confirmed by Hidden Markov Model-based search. The first half of EIL proteins (∼80–280 residues including EIN3 domain) was substantially conserved. The second half (∼300–600 residues) was considerably diverged. Additionally, first half of proteins harbored acidic, proline-rich and glutamine-rich sites, and supported the essentiality of these regions in the transcriptional-activation and protein-function. Moreover, identified six segmental and one-tandem duplications demonstrated the negative or purifying selective nature of mutations. Furthermore, expression profile analysis indicated the possibility of a crosstalk between EIN3- and EIL3-like genes, and co-expression networks implicated their interactions with very diverse panels of biological molecules.

      PubDate: 2017-06-16T08:23:07Z
      DOI: 10.1016/j.abb.2017.06.012
       
  • NMR in drug design
    • Authors: Mary J. Harner; Luciano Mueller; Kevin J. Robbins; Michael D. Reily
      Abstract: Publication date: Available online 13 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Mary J. Harner, Luciano Mueller, Kevin J. Robbins, Michael D. Reily
      The use of NMR as a tool to determine 3 dimensional protein solution structures, once a darling of the pharmaceutical industry, has largely given way to study of the interaction of prospective drugs with macromolecular targets. Many of these approaches involve ligand-centered studies, which have the advantage of speed and efficiency, but there are also many approaches that take directly from our learnings in macromolecular NMR and provide greater structural detail yet are still optimized for rapid turn-around of information. In the evolution of NMR in the pharmaceutical industry, the unique strengths of NMR to provide dynamic and atomic level information continue to be exploited to discover and design new drugs. Numerous methods have been developed over the past two decades that fall into the categories of fragment-based pre-lead discovery, ligand binding studies and qualitative structural screening.

      PubDate: 2017-06-16T08:23:07Z
      DOI: 10.1016/j.abb.2017.06.005
       
  • New NMR tools for protein structure and function: Spin tags for dynamic
           nuclear polarization solid state NMR
    • Authors: Rivkah Rogawski; Ann McDermott
      Abstract: Publication date: Available online 13 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Rivkah Rogawski, Ann McDermott
      Magic angle spinning solid state NMR studies of biological macromolecules [1–3] have enabled exciting studies of membrane proteins [4,5], amyloid fibrils [6], viruses, and large macromolecular assemblies [7]. Dynamic nuclear polarization (DNP) provides a means to enhance detection sensitivity for NMR, particularly for solid state NMR, with many recent biological applications and considerable contemporary efforts towards elaboration and optimization of the DNP experiment. This review explores precedents and innovations in biological DNP experiments, especially highlighting novel chemical biology approaches to introduce the radicals that serve as a source of polarization in the DNP experiments.

      PubDate: 2017-06-16T08:23:07Z
      DOI: 10.1016/j.abb.2017.06.010
       
  • Flavin-catalyzed redox tailoring reactions in natural product biosynthesis
    • Authors: Robin Teufel
      Abstract: Publication date: Available online 12 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Robin Teufel
      Natural products are distinct and often highly complex organic molecules that constitute not only an important drug source, but have also pushed the field of organic chemistry by providing intricate targets for total synthesis. How the astonishing structural diversity of natural products is enzymatically generated in biosynthetic pathways remains a challenging research area, which requires detailed and sophisticated approaches to elucidate the underlying catalytic mechanisms. Commonly, the diversification of precursor molecules into distinct natural products relies on the action of pathway-specific tailoring enzymes that catalyze, e.g., acylations, glycosylations, or redox reactions. This review highlights a selection of tailoring enzymes that employ riboflavin (vitamin B2)-derived cofactors (FAD and FMN) to facilitate unusual redox catalysis and steer the formation of complex natural product pharmacophores. Remarkably, several such recently reported flavin-dependent tailoring enzymes expand the classical paradigms of flavin biochemistry leading, e.g., to the discovery of the flavin-N5-oxide - a novel flavin redox state and oxygenating species.

      PubDate: 2017-06-16T08:23:07Z
      DOI: 10.1016/j.abb.2017.06.008
       
  • Ubiquitin-proteasome system and ER stress in the retina of diabetic rats
    • Authors: Karnam Shruthi; Singareddy Sreenivasa Reddy; Geereddy Bhanuprakash Reddy
      Abstract: Publication date: Available online 9 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Karnam Shruthi, Singareddy Sreenivasa Reddy, Geereddy Bhanuprakash Reddy
      Purpose Diabetic retinopathy (DR) is the most frequently occurring complication ofdiabetes. Alterations in ubiquitin–proteasome system (UPS) have been associated with several degenerative disorders. Hence, in this study, we investigated the status and role of UPS and ER stress in the retina of diabetic rats. Methods Diabetes was induced in rats by streptozotocin. Retinal markers, ER stress markers, components of UPS, ERAD, and autophagy were analyzed after 2- and 4-months of diabetes. Apoptosis was analyzed by TUNEL Assay. Results There were increased acellular capillaries and pericyte loss in diabetic rat retina. Decreased protein expression of UPS components - ubiquitin activating enzyme (E1), deubiquitinating enzymes (UCHL1 and UCHL5), SIAH1 (E3 ligase) and free ubiquitin were observed in the diabetic rats. Increased ER stress markers (ATF6, XBP1, and CHOP) and decreased expression of HRD1 in diabetic rats is associated with declined autophagy (LC3B) and apoptosis. Interestingly, treatment of diabetic rats with a chemical chaperone (4-PBA) restored the levels of DUBs and ameliorated ER stress-induced retinal cell death in type 1 diabetic rats. Conclusion The declined UPS components: E1 and HRD1 in the retina of diabetic rats could elicit ER stress, and the prolonged ER stress may trigger CHOP-mediated neuronal apoptosis.

      PubDate: 2017-06-12T07:44:26Z
      DOI: 10.1016/j.abb.2017.06.006
       
  • Structure-function studies of MICAL, the unusual multidomain flavoenzyme
           involved in actin cytoskeleton dynamics
    • Authors: Maria Antonietta Vanoni
      Abstract: Publication date: Available online 8 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Maria Antonietta Vanoni
      MICAL (from the Molecule Interacting with CasL) indicates a family of multidomain proteins conserved from insects to humans, which are increasingly attracting attention for their participation in the control of actin cytoskeleton dynamics, and, therefore, in the several related key processes in health and disease. MICAL is unique among actin binding proteins because it catalyzes a NADPH-dependent F-actin depolymerizing reaction. This unprecedented reaction is associated with its N-terminal FAD-containing domain that is structurally related to p-hydroxybenzoate hydroxylase, the prototype of aromatic monooxygenases, but catalyzes a strong NADPH oxidase activity in the free state. This review will focus on the known structural and functional properties of MICAL forms in order to provide an overview of the arguments supporting the current hypotheses on the possible mechanism of action of MICAL in the free and F-actin bound state, on the modulating effect of the CH, LIM, and C-terminal domains that follow the catalytic flavoprotein domain on the MICAL activities as well as that of small molecules and proteins interacting with MICAL.
      Graphical abstract image

      PubDate: 2017-06-12T07:44:26Z
      DOI: 10.1016/j.abb.2017.06.004
       
  • Evolution of the fusogenic activity of the receptor FGFRL1
    • Authors: Lei Zhuang; Beat Trueb
      Abstract: Publication date: Available online 5 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Lei Zhuang, Beat Trueb
      FGFRL1 is a transmembrane receptor that can induce the fusion of CHO cells to multinucleated syncytia. This cell fusion activity has been attributed to the extracellular Ig3 domain of the receptor. We investigated how the fusogenic activity evolved during the evolution of animals. We found that the Ig3 domain from humans, mice, chicken and fish stimulates fusion of CHO cells, while the Ig3 domain from lancelet and sea urchin does not. It is therefore conceivable that the fusogenic activity of FGFRL1 developed during the evolution of vertebrates. Bony fish contain two copies of the FGFRL1 gene because they have undergone a whole-genome duplication. One of the corresponding proteins (FGFRL1a) induces cell-cell fusion, while the other (FGFRL1b) does not. Analysis of chimeric constructs and in vitro mutagenesis suggested that FGFRL1b has lost its fusogenic activity after duplication. A rescue experiment supported this conclusion. When four amino acids were changed, the Ig3 domain of FGFRL1b was converted into an active, fusogenic protein comparable to FGFRL1a. The four amino acids are located in a hydrophobic pocket of the Ig3 domain. It is likely that this hydrophobic pocket interacts with a target molecule on the membrane of adjacent cells to induce cell-cell fusion.

      PubDate: 2017-06-07T07:30:27Z
      DOI: 10.1016/j.abb.2017.06.002
       
  • Hypercholesterolemia: The role of PCSK9
    • Authors: Quantil M. Melendez; Sreevidhya T. Krishnaji; Catherine J. Wooten; Dayami Lopez
      Abstract: Publication date: Available online 3 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Quantil M. Melendez, Sreevidhya T. Krishnaji, Catherine J. Wooten, Dayami Lopez
      Heart disease ends the life of more people than any other disease in the United States. High levels of low density lipoprotein (LDL)-cholesterol cause heart diseases by increasing the formation of atherosclerotic plaques. Proprotein convertase subtilisin/kexin-9 (PCSK9) indirectly regulates plasma LDL levels by controlling the LDL receptor expression at the plasma membrane. PCSK9 also appears to modulate glucose intolerance, insulin resistance, abdominal obesity, inflammation, and hypertension. The magnitude of PCSK9's involvement in the onset of these metabolic abnormalities appears to be associated with age, sex, and ethnic background. Another regulator, the inducible degrader of the LDL receptor (IDOL), works by enhancing the ubiquitination of the LDL receptor. Herein, we will review the functions and regulatory mechanisms of PCSK9. The effects of PCSK9 on the LDL receptor, the relationship of this convertase with IDOL, and treatments currently available against hypercholesterolemia are also discussed.

      PubDate: 2017-06-07T07:30:27Z
      DOI: 10.1016/j.abb.2017.06.001
       
  • Functional communication between PKC-targeted cardiac troponin I
           phosphorylation sites
    • Authors: Sarah E. Lang; Tamara K. Stevenson; Tabea M. Schatz; Brandon J. Biesiadecki; Margaret V. Westfall
      Abstract: Publication date: Available online 3 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Sarah E. Lang, Tamara K. Stevenson, Tabea M. Schatz, Brandon J. Biesiadecki, Margaret V. Westfall
      Increased protein kinase C (PKC) activity is associated with heart failure, and can target multiple cardiac troponin I (cTnI) residues in myocytes, including S23/24, S43/45 and T144. In earlier studies, cTnI-S43D and/or -S45D augmented S23/24 and T144 phosphorylation, which suggested there is communication between clusters. This communication is now explored by evaluating the impact of phospho-mimetic cTnI S43/45D combined with S23/24D (cTnIS4D) or T144D (cTnISDTD). Gene transfer of epitope-tagged cTnIS4D and cTnISDTD into adult cardiac myocytes progressively replaced endogenous cTnI. Partial replacement with cTnISDTD or cTnIS4D accelerated the time to peak (TTP) shortening and time to 50% re-lengthening (TTR50%) on day 2, but peak shortening was only diminished by cTnIS4D. Extensive cTnIS4D replacement continued to accelerate TTP, and decrease shortening amplitude, while TTR50% returned to baseline levels on day 4. In contrast, cTnISDTD modestly reduced shortening amplitude and continued to accelerate myocyte TTP and TTR50%. These results indicate cTnIS43/45 communicates with S23/24 and T144, with S23/24 exacerbating and T144 attenuating the S43/45D-dependent functional deficit. In addition, more severe functional alterations in cTnIS4D myocytes were accompanied by higher levels of secondary phosphorylation compared to cTnISDTD. These results suggest that secondary phosphorylation helps to maintain steady-state contractile function during chronic cTnI phosphorylation at PKC sites.

      PubDate: 2017-06-07T07:30:27Z
      DOI: 10.1016/j.abb.2017.05.019
       
  • MiR-491 inhibits skeletal muscle differentiation through targeting
           myomaker
    • Authors: Jian He; Fei Wang; Peng Zhang; Wenjiong Li; Jing Wang; Jinglong Li; Hongju Liu; Xiaoping Chen
      Abstract: Publication date: Available online 1 June 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Jian He, Fei Wang, Peng Zhang, Wenjiong Li, Jing Wang, Jinglong Li, Hongju Liu, Xiaoping Chen
      The myogenesis of skeletal muscle has several stages, including satellite cell proliferation, differentiation, fusion and specific muscle formation. Recent studies have shown that myomaker, a muscle-specific transmembrane protein, was critical for myoblasts fusion. However, the regulatory mechanism of myomaker and its effects on myogenesis remain elusive. In this study, miR-491 was identified as a post-transcriptional regulator of myomaker, which binds specifically to its 3′ untranslated region leading to its down-regulation. At the end of myotube differentiation, the expression levels of miR-491 increased drastically, while myomaker was significantly down-regulated, which indicated that miR-491 shut down the expression of myomaker. Functional studies showed that miR-491 overexpression suppressed muscle cell differentiation and adult muscle regeneration, while the inhibition of miR-491 promoted myotube differentiation. Taken together, our findings identified miR-491 as a novel negative regulator of myogenic differentiation through targeting myomaker.

      PubDate: 2017-06-02T07:10:45Z
      DOI: 10.1016/j.abb.2017.05.020
       
  • A singular mutation in the hemagglutinin of the 1918 pandemic virus
    • Authors: Yves-Henri Sanejouand
      Abstract: Publication date: Available online 31 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yves-Henri Sanejouand
      The influenza pandemic of 1918–1919 killed at least 50 million people. The reasons why this pandemic was so deadly remain largely unknown [9]. However, It has been shown that the 1918 viral hemagglutinin allows to reproduce the hallmarks of the illness observed during the original pandemic [11]. Thanks to the wealth of hemagglutinin sequences accumulated over the last decades, amino-acid substitutions that are found in the 1918–1919 sequences but rare otherwise can be identified with high confidence. Noteworthy, Gly 188, which is located within a key motif of the receptor binding site, has never been observed again in sequences of human viruses of subtype H1. Monitoring this singular mutation in viral sequences may help prevent another dramatic pandemic.

      PubDate: 2017-06-02T07:10:45Z
      DOI: 10.1016/j.abb.2017.05.013
       
  • The type II isopentenyl Diphosphate:Dimethylallyl diphosphate isomerase
           (IDI-2): A model for acid/base chemistry in flavoenzyme catalysis
    • Authors: Christopher J. Thibodeaux; Hung-wen Liu
      Abstract: Publication date: Available online 31 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Christopher J. Thibodeaux, Hung-wen Liu
      The chemical versatility of the flavin coenzyme is nearly unparalleled in enzyme catalysis. An interesting illustration of this versatility can be found in the reaction catalyzed by the type II isopentenyl diphosphate:dimethylallyl diphosphate isomerase (IDI-2) – an enzyme that interconverts the two essential isoprene units (isopentenyl pyrophosphate and dimethylallyl pyrophosphate) that are needed to initiate the biosynthesis of all isoprenoids. Over the past decade, a variety of biochemical, spectroscopic, structural and mechanistic studies of IDI-2 have provided mounting evidence that the flavin coenzyme of IDI-2 acts in a most unusual manner – as an acid/base catalyst to mediate a 1,3-proton addition/elimination reaction. While not entirely without precedent, IDI-2 is by far the most extensively studied flavoenzyme that employs flavin-mediated acid/base catalysis. Thus, IDI-2 serves as an important mechanistic model for understanding this often overlooked, but potentially widespread reactivity of flavin coenzymes. This review details the most pertinent studies that have contributed to the development of mechanistic proposals for this highly unusual flavoenzyme, and discusses future experiments that may be able to clarify remaining uncertainties in the chemical mechanism of IDI-2.

      PubDate: 2017-06-02T07:10:45Z
      DOI: 10.1016/j.abb.2017.05.017
       
  • Recent advances in measuring the kinetics of biomolecules by NMR
           relaxation dispersion spectroscopy
    • Authors: David Ban; Colin A. Smith; Bert L. de Groot; Christian Griesinger; Donghan Lee
      Abstract: Publication date: Available online 30 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): David Ban, Colin A. Smith, Bert L. de Groot, Christian Griesinger, Donghan Lee
      Protein function can be modulated or dictated by the amplitude and timescale of biomolecular motion, therefore it is imperative to study protein dynamics. Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful technique capable of studying timescales of motion that range from those faster than molecular reorientation on the picosecond timescale to those that occur in real-time. Across this entire regime, NMR observables can report on the amplitude of atomic motion, and the kinetics of atomic motion can be ascertained with a wide variety of experimental techniques from real-time to milliseconds and several nanoseconds to picoseconds. Still a four orders of magnitude window between several nanoseconds and tens of microseconds has remained elusive. Here, we highlight new relaxation dispersion NMR techniques that serve to cover this “hidden-time” window up to hundreds of nanoseconds that achieve atomic resolution while studying the molecule under physiological conditions.

      PubDate: 2017-06-02T07:10:45Z
      DOI: 10.1016/j.abb.2017.05.016
       
  • Unravelling the interaction of pirenzepine, a gastrointestinal disorder
           drug, with calf thymus DNA: An in vitro and molecular modelling study
    • Authors: Yusra Rahman; Shumaila Afrin Mohammed Amir Husain Tarique Sarwar Abad
      Abstract: Publication date: Available online 27 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yusra Rahman, Shumaila Afrin, Mohammed Amir Husain, Tarique Sarwar, Abad Ali, Shamsuzzaman, Mohammad Tabish
      Pirenzepine is an anti-ulcer agent which belongs to the anti-cholinergic group of gastrointestinal disorder drugs and functions as an M1 receptor selective antagonist. Drug-DNA interaction studies are of great significance as it helps in the development of new therapeutic drugs. It provides a deeper understanding into the mechanism through which therapeutic drugs control gene expression. Interaction of pirenzepine with calf-thymus DNA (Ct-DNA) was determined via a series of biophysical techniques. UV-visible absorption and fluorescence spectroscopy confirmed the formation of pirenzepine-Ct-DNA complex. The values of binding constant from various experiments were calculated to be in the order of 103 M−1 which is consistent with the groove binding mode. Various spectrofluorimetric experiments like competitive displacement of well known dyes with drug, iodide quenching experiments and the effect of Ct-DNA denaturation in presence of drug confirmed the binding of pirenzepine to the groove of Ct-DNA. The binding mode was further established by viscometric, circular dichroic and molecular modelling studies. Thermodynamic parameters obtained from isothermal titration calorimetric studies suggest that the interaction of pirenzepine with Ct-DNA is enthalpically driven. The value of TΔS and ΔH calculated from calorimetric studies were found to be 4.3 kcal mol−1 and -2.54 kcal mol−1 respectively, indicating that pirenzepine-Ct-DNA complex is mainly stabilized by hydrophobic interaction and hydrogen bonding. The binding energy calculated was −7.5 kcal mol−1 from modelling studies which was approximately similar to that obtained by isothermal titration calorimetric studies. Moreover, the role of electrostatic interaction in the binding of pirenzepine to Ct-DNA cannot be precluded.

      PubDate: 2017-05-28T06:54:22Z
       
  • The enzyme: Renalase
    • Authors: Graham Moran; Matthew Hoag
      Abstract: Publication date: Available online 27 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Graham R. Moran, Matthew R. Hoag
      Within the last two years catalytic substrates for renalase have been identified, some 10 years after its initial discovery. 2- and 6-dihydronicotinamide (2- and 6-DHNAD) isomers of β-NAD(P)H (4-dihydroNAD(P)) are rapidly oxidized by renalase to form β-NAD(P)+. The two electrons liberated are then passed to molecular oxygen by the renalase FAD cofactor forming hydrogen peroxide. This activity would appear to serve an intracellular detoxification/metabolite repair function that alleviates inhibition of primary metabolism dehydrogenases by 2- and 6-DHNAD molecules. This activity is supported by the complete structural assignment of the substrates, comprehensive kinetic analyses, defined species specific substrate specificity profiles and X-ray crystal structures that reveal ligand complexation consistent with this activity. This apparently intracellular function for the renalase enzyme is not allied with the majority of the renalase research that holds renalase to be a secreted mammalian protein that functions in blood to elicit a broad array of profound physiological changes. In this review a description of renalase as an enzyme is presented and an argument is offered that its enzymatic function can now reasonably be assumed to be uncoupled from whole organism physiological influences.

      PubDate: 2017-05-28T06:54:22Z
       
  • Nitroalkane oxidase: Structure and mechanism
    • Authors: Paul F. Fitzpatrick
      Abstract: Publication date: Available online 18 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Paul F. Fitzpatrick
      The flavoprotein nitroalkane oxidase catalyzes the oxidation of neutral nitroalkanes to the corresponding aldehydes or ketones, releasing nitrite and transferring electrons to O2 to form H2O2. A combination of solution and structural analyses have provided a detailed understanding of the mechanism of this enzyme.
      Graphical abstract image

      PubDate: 2017-05-23T04:54:15Z
      DOI: 10.1016/j.abb.2017.05.012
       
  • Applications of NMR to membrane proteins
    • Authors: Stanley J. Opella; Francesca M. Marassi
      Abstract: Publication date: Available online 18 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Stanley J. Opella, Francesca M. Marassi
      Membrane proteins present a challenge for structural biology. In this article, we review some of the recent developments that advance the application of NMR to membrane proteins, with emphasis on structural studies in detergent-free, lipid bilayer samples that resemble the native environment. NMR spectroscopy is not only ideally suited for structure determination of membrane proteins in hydrated lipid bilayer membranes, but also highly complementary to the other principal techniques based on X-ray and electron diffraction. Recent advances in NMR instrumentation, spectroscopic methods, computational methods, and sample preparations are driving exciting new efforts in membrane protein structural biology.
      Graphical abstract image

      PubDate: 2017-05-23T04:54:15Z
      DOI: 10.1016/j.abb.2017.05.011
       
  • Repulsive surfaces and lamellar lubrication of synovial joints
    • Authors: Zenon Pawlak; Kehinde Q. Yusuf; Raghuvir Pai; Wieslaw Urbaniak
      Abstract: Publication date: Available online 17 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Zenon Pawlak, Kehinde Q. Yusuf, Raghuvir Pai, Wieslaw Urbaniak
      Surface-active phospholipid (SAPL) secreted in the synovial joint plays an important role in cartilage integrity. In healthy joints, phospholipid multibilayers coat the cartilage surface, providing boundary lamellar-repulsive hydration lubrication. Current mechanism for lubrication of synovial joints, as well as the physical and chemical nature of the cartilage surface is discussed. Friction between phospholipid (PL) bilayers attached to cartilage surfaces is considered including a discussion on the recent observation of an extreme friction reduction as a consequence of a less charged hydrophilic cartilage surface. It is proposed that the highly efficient lubrication occurring in natural joints arises from the presence of negatively charged cartilage surfaces. The lamellar-repulsive mechanisms for the reduction of friction is supported by phospholipid lamellar phases and charged macromolecules residing between contacting cartilage surfaces at pH ∼7.4.
      Graphical abstract image

      PubDate: 2017-05-18T04:49:55Z
      DOI: 10.1016/j.abb.2017.05.009
       
  • The effects of troglitazone on AMPK in HepG2 cells
    • Authors: Katherine M. Allen; Kimberly A. Coughlan; Fabliha N. Mahmood; Rudy J. Valentine; Neil B. Ruderman; Asish K. Saha
      Abstract: Publication date: Available online 16 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Katherine M. Allen, Kimberly A. Coughlan, Fabliha N. Mahmood, Rudy J. Valentine, Neil B. Ruderman, Asish K. Saha
      AMP-activated protein kinase (AMPK) is an enzyme crucial in cellular metabolism found to be inhibited in many metabolic diseases including type 2 diabetes. Thiazolidinediones (TZDs) are a class of anti-diabetic drug known to activate AMPK through increased phosphorylation at Thr172, however there has been no research to date on whether they have any effect on inhibition of AMPK's lesser known site of inhibition, Ser485/491. HepG2 cells were treated with troglitazone and phosphorylation of AMPK was found to increase at both Thr172 and Ser485 in a dose- and time-dependent manner. Treatment of HepG2 cells with insulin and PMA led to increases in p-AMPK Ser485 via Akt and PKD1 respectively; however these kinases were not found to be implicated in increases seen from troglitazone. Incubation with the other TZDs, rosiglitazone and pioglitazone, let to a minor increase in p-AMPK Ser485 phosphorylation as well as AMPK activity; however these findings were significantly less than those of troglitazone under equal conditions. These data suggest that the effects of troglitazone on AMPK are more complex than previously thought. Phosphorylation at sites of both activation and inhibition can occur in tandem, although the mechanism by which this occurs has not yet been elucidated.

      PubDate: 2017-05-18T04:49:55Z
      DOI: 10.1016/j.abb.2017.05.010
       
  • Characterization of Cu(II)-reconstituted ACC Oxidase using experimental
           and theoretical approaches
    • Authors: Nadia El Bakkali-Tahéri; Sybille Tachon; Maylis Orio; Sylvain Bertaina; Marlène Martinho; Viviane Robert; Marius Réglier; Thierry Tron; Pierre Dorlet; A. Jalila Simaan
      Abstract: Publication date: Available online 15 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Nadia El Bakkali-Tahéri, Sybille Tachon, Maylis Orio, Sylvain Bertaina, Marlène Martinho, Viviane Robert, Marius Réglier, Thierry Tron, Pierre Dorlet, A. Jalila Simaan
      1-Aminocyclopropane-1-carboxylic acid oxidase (ACCO) is a non heme iron(II) containing enzyme that catalyzes the final step of the ethylene biosynthesis in plants. The iron(II) ion is bound in a facial triad composed of two histidines and one aspartate (H177, D179 and H234). Several active site variants were generated to provide alternate binding motifs and the enzymes were reconstituted with copper(II). Continuous wave (cw) and pulsed Electron Paramagnetic Resonance (EPR) spectroscopies as well as Density Functional Theory (DFT) calculations were performed and models for the copper(II) binding sites were deduced. In all investigated enzymes, the copper ion is equatorially coordinated by the two histidine residues (H177 and H234) and probably two water molecules. The copper-containing enzymes are inactive, even when hydrogen peroxide is used in peroxide shunt approach. EPR experiments and DFT calculations were undertaken to investigate substrate's (ACC) binding on the copper ion and the results were used to rationalize the lack of copper-mediated activity.
      Graphical abstract image

      PubDate: 2017-05-18T04:49:55Z
      DOI: 10.1016/j.abb.2017.03.012
       
  • Purification and site-directed mutagenesis of linoleate
           9S-dioxygenase-allene oxide synthase of Fusarium oxysporum confirms the
           oxygenation mechanism
    • Authors: Yang Chen; Fredrik Jernerén; Ernst H. Oliw
      Abstract: Publication date: Available online 11 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yang Chen, Fredrik Jernerén, Ernst H. Oliw
      Plants and fungi form jasmonic acid from α-linolenic acid. The first two steps of biosynthesis in plants occur by sequential transformation by 13S-lipoxygenase and allene oxide synthase (AOS). The biosynthesis in fungi may follow this classical scheme, but the only fungal AOS discovered so far are cytochromes P450 (CYP) fused to 8- and 9-dioxygenases (DOX). In the present report, we purified recombinant 9S-DOX-AOS of Fusarium oxysporum from cell lysate by cobalt affinity chromatography to near homogeneity and studied key residues by site-directed mutagenesis. Sequence homology with 8R-DOX-linoleate diol synthases (8R-DOX-LDS) suggested that Tyr414 catalyzes hydrogen abstraction and that Cys1051 forms the heme thiolate ligand. Site-directed mutagenesis (Tyr414Phe; Cys1051Ser) led to loss of 9S-DOX and 9S-AOS activities, respectively, but other important residues in the CYP parts of 5,8- and 7,8-LDS or 9R-AOS were not conserved. The UV-visible spectrum of 9S-DOX-AOS showed a Soret band at 409 nm, which shifted to 413 nm in the Cys1051Ser mutant. The 9S-AOS of the Tyr414Phe mutant transformed 9S-hydroperoxides of α-linolenic and linoleic acids to allene oxides/α-ketols, but it did not transform 13-hydroperoxides. We conclude that 9S- and 8R-DOX catalyze hydrogen abstraction at C-11 and C-8, respectively, by homologous Tyr residues.

      PubDate: 2017-05-13T04:27:36Z
      DOI: 10.1016/j.abb.2017.05.007
       
  • Application of NMR to studies of intrinsically disordered proteins
    • Authors: Eric B. Gibbs; Erik C. Cook; Scott A. Showalter
      Abstract: Publication date: Available online 11 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Eric B. Gibbs, Erik C. Cook, Scott A. Showalter
      The prevalence of intrinsically disordered protein regions, particularly in eukaryotic proteins, and their clear functional advantages for signaling and gene regulation have created an imperative for high-resolution structural and mechanistic studies. NMR spectroscopy has played a central role in enhancing not only our understanding of the intrinsically disordered native state, but also how that state contributes to biological function. While pathological functions associated with protein aggregation are well established, it has recently become clear that disordered regions also mediate functionally advantageous assembly into high-order structures that promote the formation of membrane-less sub-cellular compartments and even hydrogels. Across the range of functional assembly states accessed by disordered regions, post-translational modifications and regulatory macromolecular interactions, which can also be investigated by NMR spectroscopy, feature prominently. Here we will explore the many ways in which NMR has advanced our understanding of the physical-chemical phase space occupied by disordered protein regions and provide prospectus for the future role of NMR in this emerging and exciting field.
      Graphical abstract image

      PubDate: 2017-05-13T04:27:36Z
      DOI: 10.1016/j.abb.2017.05.008
       
  • Resolution of the uncertainty in the kinetic mechanism for the
           trans-3-Chloroacrylic acid dehalogenase-catalyzed reaction
    • Authors: Jamison P. Huddleston; Susan C. Wang; Kenneth A. Johnson; Christian P. Whitman
      Abstract: Publication date: Available online 10 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Jamison P. Huddleston, Susan C. Wang, Kenneth A. Johnson, Christian P. Whitman
      trans- and cis-3-Chloroacrylic acid dehalogenase (CaaD and cis-CaaD, respectively) catalyze the hydrolytic dehalogenation of their respective isomers and represent key steps in the bacterial conversion of 1,3-dichloropropene to acetaldehyde. In prior work, a kinetic mechanism for the CaaD-catalyzed reaction could not be unequivocally determined because (1) the order of product release could not be determined and (2) the fluorescence factor for the enzyme species, E*PQ (where P = bromide and Q = malonate semialdehyde, the two products of the reaction) could not be assigned. The ambiguities in the model have now been resolved by stopped-flow experiments following the reaction using an active site fluorescent probe, αY60W-CaaD and 3-bromopropiolate, previously shown to be a mechanism-based inhibitor of CaaD, coupled with the rate of bromide release in the course of CaaD inactivation. A global fit of the combined datasets provides a complete minimal model for the reaction of αY60W-CaaD and 3-bromoacrylate. In addition, the global fit produces kinetic constants for CaaD inactivation by 3-bromopropiolate and implicates the acyl bromide as the inactivating species. Finally, a comparison of the model with that for cis-CaaD shows that for both enzymes turnover is limited by product release and not chemistry.
      Graphical abstract image

      PubDate: 2017-05-13T04:27:36Z
      DOI: 10.1016/j.abb.2017.05.004
       
  • Combining NMR and small angle X-ray scattering for the study of
           biomolecular structure and dynamics
    • Authors: Haydyn D.T. Mertens; Dmitri I. Svergun
      Abstract: Publication date: Available online 10 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Haydyn D.T. Mertens, Dmitri I. Svergun
      Small-angle X-rays scattering (SAXS) and Nuclear Magnetic Resonance (NMR) are established methods to analyze the structure and structural transitions of biological macromolecules in solution. Both methods are directly applicable to near-native macromolecular solutions and allow one to study structural responses to physical and chemical changes or ligand additions. Whereas SAXS is applied to elucidate overall structure, interactions and flexibility over a wide range of particle sizes, NMR yields atomic resolution detail for moderately sized macromolecules. NMR is arguably the most powerful technique for the experimental analysis of dynamics. The joint application of these two highly complementary techniques provides an extremely useful approach that facilitates comprehensive characterization of biomacromolecular solutions.

      PubDate: 2017-05-13T04:27:36Z
      DOI: 10.1016/j.abb.2017.05.005
       
  • Thiamine potentiates chemoprotective effects of ibuprofen in DEN induced
           hepatic cancer via alteration of oxidative stress and inflammatory
           mechanism
    • Authors: Muhammad Afzal; Imran Kazmi; Ruqaiyah Khan; Poonam Rana; Vikas Kumar; Fahad A. Al-Abbasi; Mazin Zamzami; Firoz Anwar
      Abstract: Publication date: Available online 10 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Muhammad Afzal, Imran Kazmi, Ruqaiyah Khan, Poonam Rana, Vikas Kumar, Fahad A. Al-Abbasi, Mazin Zamzami, Firoz Anwar
      Present study, was an effort to scrutinize the molecular and biochemical role of ibuprofen and thiamine combination in diethylnitrosamine (DEN)-induced HCC in Wistar rats. Single intraperitoneal injection of DEN (200 mg/kg) was used for induction of HCC in rats. The rats were divided into eight various groups. DEN induced rats were treated with pure ibuprofen (40 mg/kg) and thiamine in combination for the period of 12th weeks. The protocol was terminated after the 16th week. Exposure of DEN up-regulated the levels of different serum biochemical parameters, antioxidant enzyme level, Alfa-fetoprotein (AFP) and reduced the level of High density lipoprotein (HDL) in Wistar rats along with the alteration in pro-inflammatory cytokines viz., interlukin-6 (IL-6), Tumor necrosis factor (TNF-α) and Interleukin-1β (IL-1β) with decrease in body weight. Macroscopic evaluation, revealed DEN group rats confirmed the expansion of hepatic nodules, which were reduced by the individual treatment of ibuprofen and thiamine, but the synergistic treatment of ibuprofen and thiamine confirm the significant reduction of hepatic nodules. Further, this combination possesses the significant chemoprotective effect in DEN-induced HCC by restoring the hepatic enzymes and other biomarkers along with an alteration in pro-inflammatory cytokines. The above result concludes that ibuprofen and thiamine combination possess potent anti-cancerous activity.

      PubDate: 2017-05-13T04:27:36Z
      DOI: 10.1016/j.abb.2017.05.006
       
  • Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to
           cisplatin
    • Authors: Yeqian Feng; Wen Zou; Chunhong Hu; Guiyuan Li; Shenghua Zhou; Yan He; Fang Ma; Chao Deng; Lili Sun
      Abstract: Publication date: Available online 8 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yeqian Feng, Wen Zou, Chunhong Hu, Guiyuan Li, Shenghua Zhou, Yan He, Fang Ma, Chao Deng, Lili Sun
      Cisplatin (DDP) -based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a challenge. Recent evidence highlights the crucial regulatory roles of long non-coding RNAs (lncRNA) in tumor biology. However, the roles and regulatory mechanisms of the novel lncRNA, cancer susceptibility candidate 2 (CASC2), in cervical cancer tumorigenesis and chemoresistance are poorly understood. In this study, CASC2 expression was down-regulated in cervical cancer tissues, and was related to a shorter survival time and poorer clinicopathologic features. Exogenous CACS2 alone was sufficient to inhibit cervical cancer cell proliferation and amplified DDP-induced repression of cell proliferation. A lower expression of CACS2 was observed in the DDP-resistant cervical cancer tissues, compared to DDP-sensitive cancer tissues; CACS2 overexpression could sensitize DDP-resistant cervical cancer cell (HeLa/DDP and CaSki/DDP) to DDP. Further functional experiments indicate that CASC2 upregulated PTEN expression by direct inhibiting miR-21 in the DDP-resistant cancer cells, leading to the down-regulation of p-AKT protein. In DDP-resistant cervical cancer tissues, miR-21 was up-regulated while PTEN was down-regulated. Taken together, these observations suggest CASC2 up-regulates PTEN as a ceRNA of miR-21 and plays an important role in cervical cancer sensitivity to DDP and may serve as a potential target for cancer diagnosis and treatment.

      PubDate: 2017-05-13T04:27:36Z
      DOI: 10.1016/j.abb.2017.05.001
       
  • Biomolecular NMR: Past and future
    • Authors: John L. Markley; William Milo Westler
      Abstract: Publication date: Available online 8 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): John L. Markley, William Milo Westler
      The editors of this special volume suggested this topic, presumably because of the perspective lent by our combined >90-year association with biomolecular NMR. What follows is our personal experience with the evolution of the field, which we hope will illustrate the trajectory of change over the years. As for the future, one can confidently predict that it will involve unexpected advances. Our narrative is colored by our experience in using the NMR Facility for Biomedical Studies at Carnegie-Mellon University (Pittsburgh) and in developing similar facilities at Purdue (1977–1984) and the University of Wisconsin-Madison (1984-). We have enjoyed developing NMR technology and making it available to collaborators and users of these facilities. Our group's association with the Biological Magnetic Resonance data Bank (BMRB) and with the Worldwide Protein Data Bank (wwPDB) has also been rewarding. Of course, many groups contributed to the early growth and development of biomolecular NMR, and our brief personal account certainly omits many important milestones.

      PubDate: 2017-05-13T04:27:36Z
      DOI: 10.1016/j.abb.2017.05.003
       
  • Applications of NMR and computational methodologies to study protein
           dynamics
    • Authors: Chitra Narayanan; Khushboo Bafna; Louise D. Roux; Pratul K. Agarwal; Nicolas Doucet
      Abstract: Publication date: Available online 5 May 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Chitra Narayanan, Khushboo Bafna, Louise D. Roux, Pratul K. Agarwal, Nicolas Doucet
      Overwhelming evidence now illustrates the defining role of atomic-scale protein flexibility in biological events such as allostery, cell signaling, and enzyme catalysis. Over the years, spin relaxation nuclear magnetic resonance (NMR) has provided significant insights on the structural motions occurring on multiple time frames over the course of a protein life span. The present review article aims to illustrate to the broader community how this technique continues to shape many areas of protein science and engineering, in addition to being an indispensable tool for studying atomic-scale motions and functional characterization. Continuing developments in underlying NMR technology alongside software and hardware developments for complementary computational approaches now enable methodologies to routinely provide spatial directionality and structural representations traditionally harder to achieve solely using NMR spectroscopy. In addition to its well-established role in structural elucidation, we present recent examples that illustrate the combined power of selective isotope labeling, relaxation dispersion experiments, chemical shift analyses, and computational approaches for the characterization of conformational sub-states in proteins and enzymes.
      Graphical abstract image

      PubDate: 2017-05-08T04:08:06Z
      DOI: 10.1016/j.abb.2017.05.002
       
  • Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver
           disease
    • Authors: Saut Nababan; Shin Nishiumi; Yuki Kawano; Takashi Kobayashi; Masaru Yoshida; Takeshi Azuma
      Abstract: Publication date: Available online 26 April 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Saut Nababan, Shin Nishiumi, Yuki Kawano, Takashi Kobayashi, Masaru Yoshida, Takeshi Azuma
      Background This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD). Methods We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed using HepG2 cells stimulated with recombinant human TNFα or IL1β. The expression of steatosis-, inflammation-, and fibrosis-related genes were analyzed. Plasma samples from NAFLD patients were also analyzed by LC/MS. Results The CDAHFD-fed db/db mice with hepatic steatosis, inflammation, mild fibrosis, obesity, and hypercholesterolemia displayed significantly higher hepatic and plasma levels of free adrenic acid (p < 0.05). The accumulated adrenic acid in the CDAHFD-fed db/db mice was associated with increased expression of ELOVL2 and 5, and the suppression of the acyl-CoA oxidase 1 gene during peroxisomal β-oxidation. The pretreatment of HepG2 cells with adrenic acid enhanced their cytokine-induced cytokines and chemokines mRNA expression. In NAFLD patients, the group with the highest ALT levels exhibited higher plasma adrenic acid concentrations than the other ALT groups (p-value for trend: <0.001). Conclusion Data obtained demonstrated that adrenic acid accumulation contributes to disease progression in NAFLD.

      PubDate: 2017-05-02T03:35:08Z
      DOI: 10.1016/j.abb.2017.04.009
       
  • TRIB3 downregulation enhances doxorubicin-induced cytotoxicity in gastric
           cancer cells
    • Authors: I-Jung Wu; Rong-Jaan Lin; Hsin-Chiao Wang; Tein-Ming Yuan; Show-Mei Chuang
      Abstract: Publication date: Available online 23 April 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): I-Jung Wu, Rong-Jaan Lin, Hsin-Chiao Wang, Tein-Ming Yuan, Show-Mei Chuang
      TRIB3, which is a pseudokinase known to regulate multiple pro-survival pathways, appears to be a potential therapeutic target for the treatment of human tumors. However, its precise role in cancer is controversial, as TRIB3 protein levels have been associated with both good and poor prognosis in cancer patients. Here, we investigated the significance of TRIB3 expression in the survival of gastric cancer cells exposed to anticancer drugs. We found that the tested anticancer drug, doxorubicin, induced cytotoxicity by decreasing TRIB3 transcription, which was followed by apoptotic cell death. Moreover, TRIB3 siRNA knockdown appeared to enhance doxorubicin-induced apoptosis in gastric cancer cells, concurrently with altering the expression of downstream apoptotic factors. Conversely, overexpression of TRIB3 significantly protected cells against doxorubicin-induced apoptosis. Our results indicate that downregulation of TRIB3 appears to promote cell death and enhance doxorubicin-induced apoptosis, supporting the anti-apoptotic role of TRIB3. The inductions of three classes of MAPKs failed to affect doxorubicin-mediated TRIB3 downregulation, while TRIB3 overexpression did not affect doxorubicin-induced MAPK activation. In sum, our findings indicate that TRIB3 plays an anti-apoptotic role in doxorubicin-treated gastric cancer cell lines, perhaps indicating that the status of TRIB3 expression in response to anticancer drugs, such as doxorubicin, irinotecan or oxaliplatin, may reflect the efficiency for cancer therapy.

      PubDate: 2017-04-25T03:08:37Z
      DOI: 10.1016/j.abb.2017.04.008
       
  • Abnormal lipid/lipoprotein metabolism and high plasma testosterone levels
           in male but not female aromatase-knockout mice
    • Authors: Akiko Amano; Yoshitaka Kondo; Yoshihiro Noda; Mitsuhiro Ohta; Noriaki Kawanishi; Shuichi Machida; Kazuteru Mitsuhashi; Takafumi Senmaru; Michiaki Fukui; Osamu Takaoka; Taisuke Mori; Jo Kitawaki; Masafumi Ono; Toshiji Saibara; Hiroshi Obayashi; Akihito Ishigami
      Abstract: Publication date: Available online 22 March 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Akiko Amano, Yoshitaka Kondo, Yoshihiro Noda, Mitsuhiro Ohta, Noriaki Kawanishi, Shuichi Machida, Kazuteru Mitsuhashi, Takafumi Senmaru, Michiaki Fukui, Osamu Takaoka, Taisuke Mori, Jo Kitawaki, Masafumi Ono, Toshiji Saibara, Hiroshi Obayashi, Akihito Ishigami
      Sex steroid hormones, such as estrogen and testosterone, are believed to play important roles in lipid metabolism. To elucidate the effects of estrogen depletion on lipid metabolism in male and female mice, we used aromatase-knockout (ArKO) mice, in which Cyp19 gene disruption prevented estrogen synthesis in vivo. These mice were divided into the following 4 groups: male and female ArKO mice and male and female wild-type (WT) mice. These mice were fed a normal-fat diet (13.6% fat) ad libitum. At 159 days after birth, the mice were tested for liver and plasma lipid content and hepatic hormone receptor- and lipid/lipoprotein metabolism-related gene expression. Interestingly, we found that hepatic steatosis was accompanied by markedly elevated plasma testosterone levels in male ArKO mice but not in female ArKO mice. Plasma lipoprotein profiles exhibited concurrent decreases in LDL- and small dense LDL-triglyceride (TG) levels in male ArKO mice. Moreover, male mice, but not female mice, exhibited marked elevations in androgen receptor (AR), sterol regulatory element-binding protein 1 (SREBP1), and CD36 expression. These results strongly suggest that Cyp19 gene disruption, which induces a sexually dimorphic response and high plasma testosterone levels in male mice, also induces hepatic steatosis.

      PubDate: 2017-04-25T03:08:37Z
      DOI: 10.1016/j.abb.2017.03.007
       
  • Hydroxylation of 4-hydroxyphenylethylamine derivatives by R263 variants of
           the oxygenase component of p-hydroxyphenylacetate-3-hydroxylase
    • Authors: Pirom Chenprakhon; Taweesak Dhammaraj; Rattikan Chantiwas; Pimchai Chaiyen
      Abstract: Publication date: Available online 12 March 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Pirom Chenprakhon, Taweesak Dhammaraj, Rattikan Chantiwas, Pimchai Chaiyen
      p-hydroxyphenylacetate 3-hydroxylase from Acinetobacter baumannii catalyzes the hydroxylation of p-hydroxyphenylacetate (HPA) to yield 3,4-dihydroxyphenylacetate (DHPA). In this study, we investigated whether variants of the oxygenase component (C2) could catalyze hydroxylation of 4-hydroxyphenylethylamines to synthesize catecholamine derivatives. Single turnover product analysis showed that the R263D variant can catalyze hydroxylation of tyramine to form dopamine with the highest yield (57%). The enzyme was also found to have dual substrate charge specificity because it can also maintain reasonable hydroxylation efficiency of HPA (86%). This property is different from the R263E variant, which can hydroxylate HPA (73%) but not tyramine. The R263A variant can hydroxylate HPA (72%) and tyramine to a small extent (7%). Stopped-flow experiments indicated that tyramine and HPA prefer binding to R263D after C4a-hydroperoxy-FMN formation, while tyramine cannot bind to the wild-type or R263E enzymes. Data also indicate that the hydroxylation rate constant is the rate-limiting step. The R263D variant was used as a starting enzyme for further mutation to obtain other variants for the synthesis of additional catecholamine drugs. The R263D/Y398D double mutant enzyme showed interesting results in that it was able to catalyze the hydroxylation of octopamine to form norepinephrine. However, the enzyme still lacked stereo-selectivity in its reaction.
      Graphical abstract image

      PubDate: 2017-03-12T23:13:42Z
      DOI: 10.1016/j.abb.2017.03.004
       
  • Overcoming electrostatic repulsions during amyloid assembly: Effect of pH
           and interaction with divalent metals using model peptides
    • Authors: Octavio Monasterio; Esteban Nova; Rodrigo Diaz-Espinoza
      Abstract: Publication date: Available online 10 March 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Octavio Monasterio, Esteban Nova, Rodrigo Diaz-Espinoza
      Amyloids are polypeptide aggregates involved in many pathologies including Alzheimer's disease. Amyloid assembly is a complex process affected by different interactions including hydrogen bonding, van der Waals forces and electrostatic interactions. The highly regular amyloid structure allows for an arrangement of residues that forces side chains to be closely positioned, giving rise to potentially unfavorable interactions such as electrostatic repulsions. In these cases, amyloid assembly will depend on a balance between stabilizing versus unfavorable interactions. In this study, we rationally designed several amyloid-prone model peptides that had two acidic groups and tested their assembly into amyloids under different conditions. We found that at low pH (pH 4.0), most peptides spontaneously formed amyloids whereas no or little aggregation was observed at higher pHs (pH 8.0). When divalent metals with affinity for carboxylate groups were added at millimolar concentrations, most peptides exhibited a metal-dependent switch to the amyloid state at pH 8.0. Our results show that electrostatic repulsion between amyloid-prone sequences can be overcome in conditions that affect protonation of residue side chains. Moreover, the presence of divalent metals can contribute to electrostatic shielding through specific coordination with acidic groups and thus promote amyloid assembly at near-physiological conditions.
      Graphical abstract image

      PubDate: 2017-03-12T23:13:42Z
      DOI: 10.1016/j.abb.2017.03.003
       
 
 
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