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  Subjects -> BIOLOGY (Total: 2966 journals)
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BIOCHEMISTRY (229 journals)                  1 2     

Showing 1 - 0 of 0 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: 211)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 16)
Acta Crystallographica Section D : Biological Crystallography     Hybrid Journal   (Followers: 10)
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: 17)
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: 7)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 65)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 14)
American Journal of Polymer Science     Open Access   (Followers: 24)
Amino Acids     Hybrid Journal   (Followers: 8)
Analytical Biochemistry     Hybrid Journal   (Followers: 150)
Angiogenesis     Hybrid Journal   (Followers: 3)
Annals of Clinical Biochemistry     Hybrid Journal   (Followers: 8)
Annual Review of Biochemistry     Full-text available via subscription   (Followers: 53)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 12)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 45)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 17)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 6)
Archives of Biochemistry and Biophysics     Hybrid Journal   (Followers: 21)
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: 20)
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: 26)
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: 262)
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     Full-text available via subscription   (Followers: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 5)
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: 8)
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease     Hybrid Journal   (Followers: 16)
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research     Hybrid Journal   (Followers: 6)
Biochimie     Hybrid Journal   (Followers: 7)
Biochimie Open     Open Access  
Bioconjugate Chemistry     Full-text available via subscription   (Followers: 30)
BioDrugs     Full-text available via subscription   (Followers: 8)
Bioelectrochemistry     Hybrid Journal   (Followers: 2)
Biofuels     Hybrid Journal   (Followers: 10)
Biogeochemistry     Hybrid Journal   (Followers: 12)
BioInorganic Reaction Mechanisms     Hybrid Journal   (Followers: 1)
Biokemistri     Open Access  
Biological Chemistry     Partially Free   (Followers: 24)
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: 5)
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: 22)
Chemical Engineering Journal     Hybrid Journal   (Followers: 32)
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: 5)
Chemistry & Biology     Full-text available via subscription   (Followers: 30)
Chemistry and Ecology     Hybrid Journal  
ChemTexts     Hybrid Journal  
Clinica Chimica Acta     Hybrid Journal   (Followers: 36)
Clinical Biochemist Reviews     Full-text available via subscription   (Followers: 1)
Clinical Biochemistry     Hybrid Journal   (Followers: 19)
Clinical Chemistry     Full-text available via subscription   (Followers: 68)
Clinical Chemistry and Laboratory Medicine     Hybrid Journal   (Followers: 61)
Clinical Lipidology     Full-text available via subscription   (Followers: 1)
Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology     Hybrid Journal   (Followers: 5)
Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 2)
Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology     Hybrid Journal   (Followers: 7)
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: 11)
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: 25)
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: 60)
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: 12)
Green Chemistry     Full-text available via subscription   (Followers: 9)
Histochemistry and Cell Biology     Hybrid Journal   (Followers: 4)
Indian Journal of Biochemistry and Biophysics (IJBB)     Open Access   (Followers: 3)
Indian Journal of Clinical Biochemistry     Hybrid Journal   (Followers: 1)
Indonesian Biomedical Journal     Open Access  
Insect Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 3)
International Journal of Biochemistry & Cell Biology     Hybrid Journal   (Followers: 7)
International Journal of Biochemistry and Biophysics     Open Access   (Followers: 1)
International Journal of Biological Chemistry     Open Access   (Followers: 4)
International Journal of Biomedical Nanoscience and Nanotechnology     Hybrid Journal   (Followers: 6)
International Journal of Food Contamination     Open Access  
International Journal of Plant Physiology and Biochemistry     Open Access   (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: 5)
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: 187)
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: 3)
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: 23)
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: 4)
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: 35)
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: 4)
Molecular Aspects of Medicine     Hybrid Journal   (Followers: 4)
Molecular Informatics     Hybrid Journal   (Followers: 4)
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: 6)
Natural Products and Bioprospecting     Open Access   (Followers: 3)
Nature Chemical Biology     Full-text available via subscription   (Followers: 71)
Nature Communications     Open Access   (Followers: 156)
Neurosignals     Open Access  
Novelty in Biomedicine     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)
Pharmaceutical Bioprocessing     Full-text available via subscription   (Followers: 1)
Pharmacognosy Magazine     Open Access   (Followers: 2)
Pharmacognosy Research     Open Access   (Followers: 3)

        1 2     

Journal Cover Archives of Biochemistry and Biophysics
  [SJR: 1.478]   [H-I: 138]   [21 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0003-9861 - ISSN (Online) 1096-0384
   Published by Elsevier Homepage  [3043 journals]
  • Trifluoroethanol-induced conformational transition of the C-terminal
           sterile alpha motif (SAM) of human p73
    • Authors: José L. Neira; Ana Cámara-Artigas
      Pages: 1 - 9
      Abstract: Publication date: Available online 21 February 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): José L. Neira, Ana Cámara-Artigas
      The alpha splice variant of p73 (p73α), a homologue of the tumour suppressor p53, has at its C terminus a sterile alpha motif (SAM); this domain, SAMp73, is involved in lipid binding and it is thought to mediate in protein-protein interactions. As SAMp73 is a 68-residue-long helical bundle, it could be a good model to study the (2,2,2-trifluoroethanol) TFE-induced conformational transitions of α-helical proteins. Furthermore, as SAMp73 binds to lipids through a well-known polypeptide patch, we can test whether TFE is a good mimic of lipids and membranes. To address those questions, we used several biophysical probes, namely, fluorescence, circular dichroism, 1D, 2D and 3D-NMR spectroscopies, and dynamic light scattering. The TFE-induced conformational transition of SAMp73 was complex, involving several species as detected by the biophysical probes. The last TFE-induced transition occurred at a concentration of TFE of ∼20% (v/v), where the protein lost its compactness. None of those TFE-induced species accumulated during the two-state folding of SAMp73 in aqueous solution. The final state at 40% TFE was highly helical, but its structure was not rigid. For SAMp73, TFE did not properly mimic a membrane-like environment, since at very low TFE concentrations, other residues, together with those known to interact with lipids, were also affected by the co-solvent. Comparison with studies on isolated peptides, comprising the helical regions of SAMp73, suggests that peptides were good models of the intact protein in TFE.
      Graphical abstract image

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2017.02.004
      Issue No: Vol. 619 (2017)
       
  • Thermodynamics of interactions between mammalian cytochromes P450 and b5
    • Authors: Evgeny Yablokov; Anna Florinskaya; Alexei Medvedev; Gennady Sergeev; Natallia Strushkevich; Alexander Luschik; Tatsiana Shkel; Irina Haidukevich; Andrei Gilep; Sergey Usanov; Alexis Ivanov
      Pages: 10 - 15
      Abstract: Publication date: 1 April 2017
      Source:Archives of Biochemistry and Biophysics, Volume 619
      Author(s): Evgeny Yablokov, Anna Florinskaya, Alexei Medvedev, Gennady Sergeev, Natallia Strushkevich, Alexander Luschik, Tatsiana Shkel, Irina Haidukevich, Andrei Gilep, Sergey Usanov, Alexis Ivanov
      Cytochromes P450 (CYPs) play an important role in the metabolism of xenobiotics and various endogenous substrates. Being a crucial component of the microsomal monooxygenase system, CYPs are involved in numerous protein-protein interactions. However, mechanisms underlying molecular interactions between components of the monooxygenase system still need better characterization. In this study thermodynamic parameters of paired interactions between mammalian CYPs and cytochromes b5 (CYB5) have been evaluated using a Surface Plasmon Resonance (SPR) based biosensor Biacore 3000. Analysis of 18 pairs of CYB5-CYP complexes formed by nine different isoforms of mammalian CYPs and two isoforms of human CYB5 has shown that thermodynamically these complexes can be subdivided into enthalpy-driven and entropy-driven groups. Formation of the enthalpy-driven complexes was observed in the case of microsomal CYPs allosterically regulated by CYB5 (CYB5A-CYP3A4, CYB5A-CYP3A5, CYB5A-CYP17A1). The entropy-driven complexes were formed when CYB5 had no effect on the CYP activity (CYB5A-CYP51A1, CYB5A-CYP1B1, CYB5B-CYP11A1). Results of this study suggest that such interactions determining protein clustering are indirectly linked to the monooxygenase functioning. Positive ΔH values typical for such interactions may be associated with displacement of the solvation shells of proteins upon clustering. CYB5-CYP complex formation accompanied by allosteric regulation of CYP activity by CYB5 is enthalpy-dependent.

      PubDate: 2017-03-02T23:11:53Z
      DOI: 10.1016/j.abb.2017.02.006
      Issue No: Vol. 619 (2017)
       
  • Interaction mechanism of insulin-like peptide 5 with relaxin family
           peptide receptor 4
    • Authors: Meng-Jun Hu; Dian Wei; Xiao-Xia Shao; Jia-Hui Wang; Ya-Li Liu; Zeng-Guang Xu; Zhan-Yun Guo
      Pages: 27 - 34
      Abstract: Publication date: 1 April 2017
      Source:Archives of Biochemistry and Biophysics, Volume 619
      Author(s): Meng-Jun Hu, Dian Wei, Xiao-Xia Shao, Jia-Hui Wang, Ya-Li Liu, Zeng-Guang Xu, Zhan-Yun Guo
      Insulin-like peptide 5 (INSL5) is a gut peptide hormone belonging to the insulin/relaxin superfamily. It is implicated in the regulation of food intake and glucose homeostasis by activating relaxin family peptide receptor 4 (RXFP4). Previous studies have suggested that the B-chain is important for INSL5 activity against RXFP4. However, functionalities of the B-chain residues have not yet been systematically studied. In the present work, we conducted alanine-scanning mutagenesis of the B-chain residues of human INSL5 to obtain an overview of their contributions. Binding and activation assays of these INSL5 mutants with human RXFP4 identified two essential exposed B-chain C-terminal residues (B23Arg and B24Trp) and one important exposed central B-chain residue (B16Ile). These three determinant residues together with the C-terminal carboxylate moiety probably constitute a central receptor-binding patch that forms critical hydrophobic and electrostatic interactions with RXFP4 during INSL5 binding. Some other exposed residues, including B10Glu, B12Ile, B13Arg, B17Tyr, B21Ser, and B22Ser, made minor contributions to INSL5 function. These auxiliary residues are scattered around the edge of the central receptor-binding patch, and thus form a peripheral receptor-binding patch on the surface of INSL5. Our present work provides new insights into the interaction mechanism of INSL5 with its receptor RXFP4.
      Graphical abstract image

      PubDate: 2017-03-08T23:12:59Z
      DOI: 10.1016/j.abb.2017.03.001
      Issue No: Vol. 619 (2017)
       
  • Corrigendum to “Conformational status of cytochrome c upon
           N-homocysteinylation: Implications to cytochrome c release”
           [Arch. Biochem. Biophys. 614 (2017) 23–27]
    • Authors: Gurumayum Suraj Sharma; Laishram Rajendrakumar Singh
      First page: 44
      Abstract: Publication date: 15 March 2017
      Source:Archives of Biochemistry and Biophysics, Volume 618
      Author(s): Gurumayum Suraj Sharma, Laishram Rajendrakumar Singh


      PubDate: 2017-03-02T23:11:53Z
      DOI: 10.1016/j.abb.2017.02.002
      Issue No: Vol. 618 (2017)
       
  • A scalable lysyl hydroxylase 2 expression system and luciferase-based
           enzymatic activity assay
    • Authors: Hou-Fu Guo; Eun Jeong Cho; Ashwini K. Devkota; Yulong Chen; William Russell; George N. Phillips; Mitsuo Yamauchi; Kevin N. Dalby; Jonathan M. Kurie
      Pages: 45 - 51
      Abstract: Publication date: Available online 20 February 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Hou-Fu Guo, Eun Jeong Cho, Ashwini K. Devkota, Yulong Chen, William Russell, George N. Phillips, Mitsuo Yamauchi, Kevin N. Dalby, Jonathan M. Kurie
      Hydroxylysine aldehyde-derived collagen cross-links (HLCCs) accumulate in fibrotic tissues and certain types of cancer and are thought to drive the progression of these diseases. HLCC formation is initiated by lysyl hydroxylase 2 (LH2), an Fe(II) and α-ketoglutarate (αKG)-dependent oxygenase that hydroxylates telopeptidyl lysine residues on collagen. Development of LH2 antagonists for the treatment of these diseases will require a reliable source of recombinant LH2 protein and a non-radioactive LH2 enzymatic activity assay that is amenable to high throughput screens of small molecule libraries. However, LH2 protein generated previously using E coli– or insect-based expression systems was either insoluble or enzymatically unstable, and LH2 enzymatic activity assays have measured radioactive CO2 released from 14C-labeled αKG during its conversion to succinate. To address these deficiencies, we have developed a scalable process to purify human LH2 protein from Chinese hamster ovary cell-derived conditioned media samples and a luciferase-based assay that quantifies LH2-dependent conversion of αKG to succinate. These methodologies may be applicable to other Fe(II) and αKG-dependent oxygenase systems.

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2017.02.003
      Issue No: Vol. 618 (2017)
       
  • Signaling by sulfur-containing molecules. Quantitative aspects
    • Authors: Willem H. Koppenol; Patricia L. Bounds
      Pages: 3 - 8
      Abstract: Publication date: 1 March 2017
      Source:Archives of Biochemistry and Biophysics, Volume 617
      Author(s): Willem H. Koppenol, Patricia L. Bounds
      There is currently interest in sulfur-containing molecules that may or may not play a role in signaling. We have collected relevant thermodynamic data, namely standard Gibbs energies of formation and electrode potentials at pH 7, and used these to construct a Frost diagram. Thermodynamic data not available in the literature could be estimated with reasonable confidence. At pH 7, the electrode potential of the RSS/RSS− couple is +0.68 V, 0.28 V less than that of the RS, H+/RSH couple. S2 − is unstable with respect to HSS− and S2. Generally, polysulfur compounds, with the exception of RSSR, are thermodynamically unstable with respect to disproportionation and ultimately lead to formation of kinetically inert S8(s). About thermoneutral is the formation of RSS− from RSSR and HS−, but formation of HNO from HS− and SNO−, and from HS− and RSNO, is unfavorable. The formation of SSNO− in vivo is kinetically unlikely.
      Graphical abstract image

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2016.09.012
      Issue No: Vol. 617 (2017)
       
  • Biological chemistry of hydrogen sulfide and persulfides
    • Authors: Ernesto Cuevasanta; Matías N. Möller; Beatriz Alvarez
      Pages: 9 - 25
      Abstract: Publication date: 1 March 2017
      Source:Archives of Biochemistry and Biophysics, Volume 617
      Author(s): Ernesto Cuevasanta, Matías N. Möller, Beatriz Alvarez
      Hydrogen sulfide (H2S) has been traditionally considered to be a toxic molecule for mammals. However, it can be formed endogenously and exert physiological effects with potential health benefits. H2S can partition two-fold in biological membranes and traverse them rapidly, diffusing between compartments. H2S reactivity has similarities to that of thiols, although it is less nucleophilic than thiols and it can form different products. H2S can react with oxidants derived from the partial reduction of oxygen, but direct scavenging is unlikely to explain H2S protective actions. Important effects are exerted on mitochondria including the stimulation or the inhibition of the electron transport chain. Possible mechanisms for unleashing biological consequences are the reactions with metal centers and with thiol oxidation products. The reactions of H2S with disulfides (RSSR) and sulfenic acids (RSOH) lead to the formation of persulfides (RSSH). Persulfides have enhanced nucleophilicity with respect to the corresponding thiol, consistent with the alpha effect. Besides, the inner and outer sulfurs can both act as electrophiles. In this review, we describe the reactions of H2S with oxidized thiol products and the properties of the persulfides formed in the context of the chemical biology of H2S.
      Graphical abstract image

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2016.09.018
      Issue No: Vol. 617 (2017)
       
  • Protein cysteine oxidation in redox signaling: Caveats on sulfenic acid
           detection and quantification
    • Authors: Henry Jay Forman; Michael J. Davies; Anna C. Krämer; Giovanni Miotto; Mattia Zaccarin; Hongqiao Zhang; Fulvio Ursini
      Pages: 26 - 37
      Abstract: Publication date: 1 March 2017
      Source:Archives of Biochemistry and Biophysics, Volume 617
      Author(s): Henry Jay Forman, Michael J. Davies, Anna C. Krämer, Giovanni Miotto, Mattia Zaccarin, Hongqiao Zhang, Fulvio Ursini
      Oxidation of critical signaling protein cysteines regulated by H2O2 has been considered to involve sulfenic acid (RSOH) formation. RSOH may subsequently form either a sulfenyl amide (RSNHR′) with a neighboring amide, or a mixed disulfide (RSSR′) with another protein cysteine or glutathione. Previous studies have claimed that RSOH can be detected as an adduct (e.g., with 5,5-dimethylcyclohexane-1,3-dione; dimedone). Here, kinetic data are discussed which indicate that few proteins can form RSOH under physiological signaling conditions. We also present experimental evidence that indicates that (1) dimedone reacts rapidly with sulfenyl amides, and more rapidly than with sulfenic acids, and (2) that disulfides can react reversibly with amides to form sulfenyl amides. As some proteins are more stable as the sulfenyl amide than as a glutathionylated species, the former may account for some of the species previously identified as the “sulfenome” - the cellular complement of reversibly-oxidized thiol proteins generated via sulfenic acids.
      Graphical abstract image

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2016.09.013
      Issue No: Vol. 617 (2017)
       
  • Recent developments in detection of superoxide radical anion and hydrogen
           peroxide: Opportunities, challenges, and implications in redox signaling
    • Authors: Balaraman Kalyanaraman; Micael Hardy; Radoslaw Podsiadly; Gang Cheng; Jacek Zielonka
      Pages: 38 - 47
      Abstract: Publication date: 1 March 2017
      Source:Archives of Biochemistry and Biophysics, Volume 617
      Author(s): Balaraman Kalyanaraman, Micael Hardy, Radoslaw Podsiadly, Gang Cheng, Jacek Zielonka
      In this review, some of the recent developments in probes and assay techniques specific for superoxide (O2 –) and hydrogen peroxide (H2O2) are discussed. Over the last decade, significant progress has been made in O2 – and H2O2 detection due to syntheses of new redox probes, better understanding of their chemistry, and development of specific and sensitive assays. For superoxide detection, hydroethidine (HE) is the most suitable probe, as the product, 2-hydroxyethidium, is specific for O2 –. In addition, HE-derived dimeric products are specific for one-electron oxidants. As red-fluorescent ethidium is always formed from HE intracellularly, chromatographic techniques are required for detecting 2-hydroxyethidium. HE analogs, Mito-SOX and hydropropidine, exhibit the same reaction chemistry with O2 – and one-electron oxidants. Thus, mitochondrial superoxide can be unequivocally detected using HPLC-based methods and not by fluorescence microscopy. Aromatic boronate-based probes react quantitatively with H2O2, forming a phenolic product. However, peroxynitrite and hypochlorite react more rapidly with boronates, forming the same product. Using ROS-specific probes and HPLC assays, it is possible to screen chemical libraries to discover specific inhibitors of NADPH oxidases. We hope that rigorous detection of O2 – and H2O2 in different cellular compartments will improve our understanding of their role in redox signaling.
      Graphical abstract image

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2016.08.021
      Issue No: Vol. 617 (2017)
       
  • Selenium and redox signaling
    • Authors: Regina Brigelius-Flohé; Leopold Flohé
      Pages: 48 - 59
      Abstract: Publication date: 1 March 2017
      Source:Archives of Biochemistry and Biophysics, Volume 617
      Author(s): Regina Brigelius-Flohé, Leopold Flohé
      Selenium compounds that contain selenol functions or can be metabolized to selenols are toxic via superoxide and H2O2 generation, when ingested at dosages beyond requirement. At supra-nutritional dosages various forms of programmed cell death are observed. At physiological intakes, selenium exerts its function as constituent of selenoproteins, which overwhelmingly are oxidoreductases. Out of those, the glutathione peroxidases counteract hydroperoxide-stimulated signaling cascades comprising inflammation triggered by cytokines or lipid mediators, insulin signaling and different forms of programmed cell death. Similar events are exerted by peroxiredoxins, which functionally depend on the selenoproteins of the thioredoxin reductase family. The thiol peroxidases of both families can, however, also act as sensors for hydroperoxides, thereby initiating signaling cascades. Although the interaction of selenoproteins with signaling events has been established by genetic techniques, the in vivo relevance of these findings is still hard to delineate for several reasons: The biosynthesis of individual selenoproteins responds differently to variations of selenium intakes; selenium is preferentially delivered to privileged tissues via inter-organ trafficking and receptor-mediated uptake, and only half of the selenoproteins known by sequence have been functionally characterized. The fragmentary insights do not allow any uncritical use of selenium for optimizing human health.

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2016.08.003
      Issue No: Vol. 617 (2017)
       
  • The role of peroxiredoxin 1 in redox sensing and transducing
    • Authors: Elizabeth C. Ledgerwood; James W.A. Marshall; Johannes F. Weijman
      Pages: 60 - 67
      Abstract: Publication date: 1 March 2017
      Source:Archives of Biochemistry and Biophysics, Volume 617
      Author(s): Elizabeth C. Ledgerwood, James W.A. Marshall, Johannes F. Weijman
      Peroxiredoxin 1 is a member of the ubiquitous peroxiredoxin family of thiol peroxidases that catalyse the reduction of peroxides. In recent years eukaryotic peroxiredoxins have emerged as a critical component of cellular redox signalling, particularly in response to alterations in production of hydrogen peroxide. Peroxiredoxins are exquisitely sensitive to oxidation by hydrogen peroxide making them key peroxide sensing enzymes within cells. Evidence gathered over the last decade suggests that in addition to sensing the redox signal, peroxiredoxins have a major role in transducing this signal to downstream signalling proteins, ultimately contributing to regulation of diverse cellular processes including proliferation, differentiation and apoptosis. In this review we present the three current models for the sensing and signal transducing roles of peroxiredoxins, with a specific focus on mammalian peroxiredoxin 1. The evidence for each mechanism is discussed and areas for future work are identified.

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2016.10.009
      Issue No: Vol. 617 (2017)
       
  • Keap1, the cysteine-based mammalian intracellular sensor for electrophiles
           and oxidants
    • Authors: Albena T. Dinkova-Kostova; Rumen V. Kostov; Peter Canning
      Pages: 84 - 93
      Abstract: Publication date: 1 March 2017
      Source:Archives of Biochemistry and Biophysics, Volume 617
      Author(s): Albena T. Dinkova-Kostova, Rumen V. Kostov, Peter Canning
      The Kelch-like ECH associated protein 1 (Keap1) is a component of a Cullin3-based Cullin-RING E3 ubiquitin ligase (CRL) multisubunit protein complex. Within the CRL, homodimeric Keap1 functions as the Cullin3 adaptor, and importantly, it is also the critical component of the E3 ligase that performs the substrate recognition. The best-characterized substrate of Keap1 is transcription factor NF-E2 p45-related factor 2 (Nrf2), which orchestrates an elaborate transcriptional program in response to environmental challenges caused by oxidants, electrophiles and pro-inflammatory agents, allowing adaptation and survival under stress conditions. Keap1 is equipped with reactive cysteine residues that act as sensors for endogenously produced and exogenously encountered small molecules (termed inducers), which have a characteristic chemical signature, reactivity with sulfhydryl groups. Inducers modify the cysteine sensors of Keap1 and impair its ability to target Nrf2 for ubiquitination and degradation. Consequently, Nrf2 accumulates, enters the nucleus and drives the transcription of its target genes, which encode a large network of cytoprotective proteins. Here we summarize the early studies leading to the prediction of the existence of Keap1, followed by the discovery of Keap1 as the main negative regulator of Nrf2. We then describe the available structural information on Keap1, its assembly with Cullin3, and its interaction with Nrf2. We also discuss the multiple cysteine sensors of Keap1 that allow for detection of a wide range of endogenous and environmental inducers, and provide fine-tuning and tight control of the Keap1/Nrf2 stress-sensing response.

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2016.08.005
      Issue No: Vol. 617 (2017)
       
  • Keap1 as the redox sensor of the antioxidant response
    • Authors: Virve Sihvola; Anna-Liisa Levonen
      Pages: 94 - 100
      Abstract: Publication date: 1 March 2017
      Source:Archives of Biochemistry and Biophysics, Volume 617
      Author(s): Virve Sihvola, Anna-Liisa Levonen
      Reactive oxygen species (ROS) and products of their reactions with cellular macromolecules such as unsaturated fatty acids have been implicated to be important regulators of signalling processes via oxidation or alkylation of redox active thiol residues in target proteins. One of key redox-sensitive signalling proteins mediating the response to oxidant stress is Keap1 (Kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1), which is a negative regulator of transcription factor Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and the central hub for sensing endogenous and environmental oxidative and electrophilic stress. In this review, we provide an overview of the mechanisms by which Keap1 orchestrates the antioxidant response and how the system can be targeted for therapy.

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2016.10.010
      Issue No: Vol. 617 (2017)
       
  • Thioredoxin and redox signaling: Roles of the thioredoxin system in
           control of cell fate
    • Authors: Atsushi Matsuzawa
      Pages: 101 - 105
      Abstract: Publication date: 1 March 2017
      Source:Archives of Biochemistry and Biophysics, Volume 617
      Author(s): Atsushi Matsuzawa
      Reactive oxygen species (ROS) are not only cytotoxic products from external and internal environment, but also important mediators of redox signaling. Therefore, thioredoxin (Trx) as an antioxidant maintains the balance of the thiol-related redox status, and also plays pivotal roles in the regulation of redox signaling. Trx senses and responds to environmental oxidative stress and ROS generated by cellular respiration, metabolism, and immune response, and then modulates the redox status, function, and activity of its target signaling proteins. Dysregulation of such the Trx system affects various cellular functions and cell fate such as survival and cell death, leading to human diseases including cancer and inflammation. This review focuses on Trx and its target proteins involved in redox signaling, which are critical for the control of cell fate such as cell survival and apoptosis, and addresses how Trx regulates those effector proteins and redox signaling.

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2016.09.011
      Issue No: Vol. 617 (2017)
       
  • Protein disulfide isomerases: Redox connections in and out of the
           endoplasmic reticulum
    • Authors: Ana Iochabel Soares Moretti; Francisco Rafael Martins Laurindo
      Pages: 106 - 119
      Abstract: Publication date: 1 March 2017
      Source:Archives of Biochemistry and Biophysics, Volume 617
      Author(s): Ana Iochabel Soares Moretti, Francisco Rafael Martins Laurindo
      Protein disulfide isomerases are thiol oxidoreductase chaperones from thioredoxin superfamily. As redox folding catalysts from the endoplasmic reticulum (ER), their roles in ER-related redox homeostasis and signaling are well-studied. PDIA1 exerts thiol oxidation/reduction and isomerization, plus chaperone effects. Also, substantial evidence indicates that PDIs regulate thiol-disulfide switches in other cell locations such as cell surface and possibly cytosol. Subcellular PDI translocation routes remain unclear and seem Golgi-independent. The list of signaling and structural proteins reportedly regulated by PDIs keeps growing, via thiol switches involving oxidation, reduction and isomerization, S-(de)nytrosylation, (de)glutathyonylation and protein oligomerization. PDIA1 is required for agonist-triggered Nox NADPH oxidase activation and cell migration in vascular cells and macrophages, while PDIA1-dependent cytoskeletal regulation appears a converging pathway. Extracellularly, PDIs crucially regulate thiol redox signaling of thrombosis/platelet activation, e.g., integrins, and PDIA1 supports expansive caliber remodeling during injury repair via matrix/cytoskeletal organization. Some proteins display regulatory PDI-like motifs. PDI effects are orchestrated by expression levels or post-translational modifications. PDI is redox-sensitive, although probably not a mass-effect redox sensor due to kinetic constraints. Rather, the “all-in-one” organization of its peculiar redox/chaperone properties likely provide PDIs with precision and versatility in redox signaling, making them promising therapeutic targets.

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2016.11.007
      Issue No: Vol. 617 (2017)
       
  • Redox status in a model of cancer stem cells
    • Authors: Mattia Zaccarin; Valentina Bosello-Travain; Maria Luisa Di Paolo; Marco Falda; Matilde Maiorino; Giovanni Miotto; Stefano Piccolo; Antonella Roveri; Fulvio Ursini; Rina Venerando; Stefano Toppo
      Pages: 120 - 128
      Abstract: Publication date: 1 March 2017
      Source:Archives of Biochemistry and Biophysics, Volume 617
      Author(s): Mattia Zaccarin, Valentina Bosello-Travain, Maria Luisa Di Paolo, Marco Falda, Matilde Maiorino, Giovanni Miotto, Stefano Piccolo, Antonella Roveri, Fulvio Ursini, Rina Venerando, Stefano Toppo
      Reversible oxidation of Cys residues is a crucial element of redox homeostasis and signaling. According to a popular concept in oxidative stress signaling, the oxidation of targets of signals can only take place following an overwhelming of the cellular antioxidant capacity. This concept, however, ignores the activation of feedback mechanisms possibly leading to a paradoxical effect. In a model of cancer stem cells (CSC), stably overexpressing the TAZ oncogene, we observed that the increased formation of oxidants is associated with a globally more reduced state of proteins. Redox proteomics revealed that several proteins, capable of undergoing reversible redox transitions, are indeed more reduced while just few are more oxidized. Among the proteins more oxidized, G6PDH emerges as both more expressed and activated by oxidation. This accounts for the observed more reduced state of the NADPH/NADP+ couple. The dynamic redox flux generating this apparently paradoxical effect is rationalized in a computational system biology model highlighting the crucial role of G6PDH activity on the rate of redox transitions eventually leading to the reduction of reversible redox switches.

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2016.09.002
      Issue No: Vol. 617 (2017)
       
  • The chemical biology of HNO signaling
    • Authors: Christopher L. Bianco; John P. Toscano; Michael D. Bartberger; Jon M. Fukuto
      Pages: 129 - 136
      Abstract: Publication date: 1 March 2017
      Source:Archives of Biochemistry and Biophysics, Volume 617
      Author(s): Christopher L. Bianco, John P. Toscano, Michael D. Bartberger, Jon M. Fukuto
      Nitroxyl (HNO) is a simple molecule with significant potential as a pharmacological agent. For example, its use in the possible treatment of heart failure has received recent attention due to its unique therapeutic properties. Recent progress has been made on the elucidation of the mechanisms associated with its biological signaling. Importantly, the biochemical mechanisms described for HNO bioactivity are consistent with its unique and novel chemical properties/reactivity. To date, much of the biology of HNO can be associated with interactions and modification of important regulatory thiol proteins. Herein will be provided a description of HNO chemistry and how this chemistry translates to some of its reported biological effects.

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2016.08.014
      Issue No: Vol. 617 (2017)
       
  • How are nitrosothiols formed de novo in vivo?
    • Authors: Jack R. Lancaster
      Pages: 137 - 144
      Abstract: Publication date: 1 March 2017
      Source:Archives of Biochemistry and Biophysics, Volume 617
      Author(s): Jack R. Lancaster
      The biological mechanisms of de novo formation of cellular nitrosothiols (as opposed to transnitrosation) are reviewed. The approach is to introduce chemical foundations for each mechanism, followed by evidence in biological systems. The general categories include mechanisms involving nitrous acid, NO autoxidation and oxidant stress, redox active and inactive metal ions, and sulfide/persulfide. Important conclusions/speculations are that de novo cellular thiol nitrosation (1) is an oxidative process, and so should be considered within the family of other thiol oxidative modifications, (2) may not involve a single dominant process but depends on the specific conditions, (3) does not involve O2 under at least some conditions, and (4) may serve to provide a “substrate pool” of protein cysteine nitrosothiol which could, through subsequent enzymatic transnitrosation/denitrosation, be “rearranged” to accomplish the specificity and regulatory control required for effective post-translational signaling.

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2016.10.015
      Issue No: Vol. 617 (2017)
       
  • Signaling by 4-hydroxy-2-nonenal: Exposure protocols, target selectivity
           and degradation
    • Authors: Hongqiao Zhang; Henry Jay Forman
      Pages: 145 - 154
      Abstract: Publication date: 1 March 2017
      Source:Archives of Biochemistry and Biophysics, Volume 617
      Author(s): Hongqiao Zhang, Henry Jay Forman
      4-hydroxy-2-nonenal (HNE), a major non-saturated aldehyde product of lipid peroxidation, has been extensively studied as a signaling messenger. In these studies a wide range of HNE concentrations have been used, ranging from the unstressed plasma concentration to far beyond what would be found in actual pathophysiological condition. In addition, accumulating evidence suggest that signaling protein modification by HNE is specific with only those proteins with cysteine, histidine, and lysine residues located in certain sequence or environments adducted by HNE. HNE-signaling is further regulated through the turnover of HNE-signaling protein adducts through proteolytic process that involve proteasomes, lysosomes and autophagy. This review discusses the HNE concentrations and exposure modes used in signaling studies, the selectivity of the HNE-adduction site, and the turnover of signaling protein adducts.

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2016.11.003
      Issue No: Vol. 617 (2017)
       
  • Anti-inflammatory signaling actions of electrophilic nitro-arachidonic
           acid in vascular cells and astrocytes
    • Authors: Andrés Trostchansky; Homero Rubbo
      Pages: 155 - 161
      Abstract: Publication date: 1 March 2017
      Source:Archives of Biochemistry and Biophysics, Volume 617
      Author(s): Andrés Trostchansky, Homero Rubbo
      Nitrated derivatives of unsaturated fatty acids (nitro-fatty acids) are being formed and detected in human plasma, cell membranes and tissue, triggering signaling cascades via covalent and reversible post-translational modifications of nucleophilic amino acids in transcriptional regulatory proteins. Arachidonic acid (AA) represents a precursor of potent signaling molecules, i.e., prostaglandins and thromboxanes through enzymatic and non-enzymatic oxidative pathways. Arachidonic acid can be nitrated by reactive nitrogen species leading to the formation of nitro-arachidonic acid (NO2-AA). A critical issue is the influence of NO2-AA on prostaglandin endoperoxide H synthases, modulating inflammatory processes through redirection of AA metabolism and signaling. In this prospective article, we describe the key chemical and biochemical actions of NO2-AA in vascular and astrocytes. This includes the ability of NO2-AA to mediate unique redox signaling anti-inflammatory actions along with its therapeutic potential.

      PubDate: 2017-02-23T16:50:05Z
      DOI: 10.1016/j.abb.2016.10.003
      Issue No: Vol. 617 (2017)
       
  • Structure and biochemistry of phenylacetaldehyde dehydrogenase from the
           Pseudomonas putida S12 styrene catabolic pathway
    • Authors: Anders G. Crabo; Baljit Singh; Tim Nguyen; Shahram Emami; George T. Gassner; Matthew H. Sazinsky
      Pages: 47 - 58
      Abstract: Publication date: 15 February 2017
      Source:Archives of Biochemistry and Biophysics, Volume 616
      Author(s): Anders G. Crabo, Baljit Singh, Tim Nguyen, Shahram Emami, George T. Gassner, Matthew H. Sazinsky
      Phenylacetaldehyde dehydrogenase catalyzes the NAD+-dependent oxidation of phenylactealdehyde to phenylacetic acid in the styrene catabolic and detoxification pathway of Pseudomonas putida (S12). Here we report the structure and mechanistic properties of the N-terminally histidine-tagged enzyme, NPADH. The 2.83 Å X-ray crystal structure is similar in fold to sheep liver cytosolic aldehyde dehydrogenase (ALDH1), but has unique set of intersubunit interactions and active site tunnel for substrate entrance. In solution, NPADH occurs as 227 kDa homotetramer. It follows a sequential reaction mechanism in which NAD+ serves as both the leading substrate and homotropic allosteric activator. In the absence of styrene monooxygenase reductase, which regenerates NAD+ from NADH in the first step of styrene catabolism, NPADH is inhibited by a ternary complex involving NADH, product, and phenylacetaldehyde, substrate. Each oligomerization domain of NPADH contains a six-residue insertion that extends this loop over the substrate entrance tunnel of a neighboring subunit, thereby obstructing the active site of the adjacent subunit. This feature could be an important factor in the homotropic activation and product inhibition mechanisms. Compared to ALDH1, the substrate channel of NPADH is narrower and lined with more aromatic residues, suggesting a means for enhancing substrate specificity.

      PubDate: 2017-02-05T11:25:21Z
      DOI: 10.1016/j.abb.2017.01.011
      Issue No: Vol. 616 (2017)
       
  • Time resolved calorimetry of photo-induced folding in horse heart
           cytochrome c at high pH
    • Authors: Tarah A. Word; Randy W. Larsen
      Pages: 10 - 14
      Abstract: Publication date: 1 February 2017
      Source:Archives of Biochemistry and Biophysics, Volume 615
      Author(s): Tarah A. Word, Randy W. Larsen
      Here the molar volume and enthalpy changes associated with the early events in the folding of ferrocytochrome c (Cc) at high pH have been examined using time resolved photoacoustic calorimetry (PAC). The data reveal an overall volume change of 1.3 ± 0.3 mL mol−1 and an enthalpy change of 13 ± 7 kcal mol −1 occurring subsequent to photodissociation of the unfolded CO bound Cc species in <∼20 ns. Two additional kinetic phases are observed that are associated with non-native His binding (ΔH and ΔV of 2 ± 4 kcal mol−1 and -0.5 mL mol−1, τ ∼ 2.5 μs ) and Met binding (ΔH and ΔV -0.4 ± 2 kcal mol−1 and -0.1 ± 0.1 mL mol−1, τ∼ 660 ns). Considering only protein conformational changes (excluding volume and enthalpies associated with heme ligation events) the initial conformational event exhibits a ΔH and ΔV of 6 ± 3 kcal mol−1 and -3±0.1 mL mol−1, respectively, that are attributed to a small contraction of the unfolded protein. The corresponding enthalpy associated with both native and non-native ligand binding are found to be −5±4 kcal mol−1 (Fe-Met) and +20 ± 4 kcal mol−1 (Fe-His) with the change in volume for both phases being essential negligible. This would indicate that non-native ligand binding likely occurs from an already collapsed conformation.
      Graphical abstract image

      PubDate: 2017-01-07T16:29:04Z
      DOI: 10.1016/j.abb.2016.12.013
      Issue No: Vol. 615 (2017)
       
  • The self-sufficient CYP102 family enzyme, Krac9955, from Ktedonobacter
           racemifer DSM44963 acts as an alkyl- and alkyloxy-benzoic acid hydroxylase
           
    • Authors: Natasha K. Maddigan; Stephen G. Bell
      Pages: 15 - 21
      Abstract: Publication date: 1 February 2017
      Source:Archives of Biochemistry and Biophysics, Volume 615
      Author(s): Natasha K. Maddigan, Stephen G. Bell
      A self-sufficient CYP102 family encoding gene (Krac_9955) has been identified from the bacterium Ktedonobacter racemifer DSM44963 which belongs to the Chloroflexi phylum. The characterisation of the substrate range of this enzyme was hampered by low levels of production using E. coli. The yield and purity of the Krac9555 enzyme was improved using a codon optimised gene, the introduction of a tag and modification of the purification protocol. The heme domain was isolated and in vitro analysis of substrate binding and turnover was performed. Krac9955 was found to preferentially bind alkyl- and alkyloxy-benzoic acids (≥95% high spin, K d  < 3 μM) over saturated and unsaturated fatty acids. Unusually for a self-sufficient CYP102 family member Krac9955 showed low levels of NAD(P)H oxidation activity for all the substrates tested though product formation was observed for many. For nearly all substrates the preferred site of hydroxylation of Krac9955 was eight carbons away from the carboxylate group with certain reactions proceeding at ≥ 90% selectivity. Krac9955 differs from CYP102A1 (P450Bm3), and is the first self-sufficient member of the CYP102 family of P450 enzymes which is not optimised for fast fatty acid hydroxylation close to the ω-terminus.

      PubDate: 2017-01-07T16:29:04Z
      DOI: 10.1016/j.abb.2016.12.014
      Issue No: Vol. 615 (2017)
       
  • Interaction of AR and iNOS in lens epithelial cell: A new pathogenesis and
           potential therapeutic targets of diabetic cataract
    • Authors: Xue Li; Wenping Liu; Xinduo Huang; Jianping Xiong; Xiaoyong Wei
      Pages: 44 - 52
      Abstract: Publication date: 1 February 2017
      Source:Archives of Biochemistry and Biophysics, Volume 615
      Author(s): Xue Li, Wenping Liu, Xinduo Huang, Jianping Xiong, Xiaoyong Wei
      Although there is significant interest in revealing the role of aldose reductase (AR) and inducible nitric oxide synthase (iNOS) in diabetic cataract (DC), the interaction of AR and iNOS remains unknown. The aim of this study is to investigate the pathogenesis mechanisms and explore as a new potential therapeutic targets for DC. This study investigated the interaction of AR-iNOS through the methods of enzyme kinetics, molecular docking and molecular dynamics simulation, co-immunoprecipitation and fluorescence resonance energy transfer (FRET). The IC50 of AR for inhibition of iNOS activity is 0.04 μM, and the IC50 of iNOS for inhibition of AR activity is 0.042 μM through enzyme kinetics; the interface showed that ARG99 on AR and GLU317 on iNOS played the key roles in the interaction of AR-iNOS predicted by molecular docking and molecular dynamics simulation. Co-immunoprecipitation of protein complexes in human lens epithelial cell (HLEC) demonstrated that AR could association with iNOS in cell; and the interaction distance of AR-iNOS was 6.50 ± 0.22 nm detected by FRET. This study exhibited a direct inhibition interaction between AR and iNOS in HLECs. It is the first report of inhibition interaction between AR and iNOS, suggesting a new pathophysiological mechanism and providing a new insight into the therapeutic mechanism of DC.
      Graphical abstract image

      PubDate: 2017-01-22T17:25:09Z
      DOI: 10.1016/j.abb.2017.01.007
      Issue No: Vol. 615 (2017)
       
  • 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
       
  • Minimized natural versions of fungal ribotoxins show improved active site
           plasticity
    • Authors: Moisés Maestro-López; Miriam Olombrada; Lucía García-Ortega; Daniel Serrano-González; Javier Lacadena; Mercedes Oñaderra; José G. Gavilanes; Álvaro Martínez-del-Pozo
      Abstract: Publication date: Available online 7 March 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Moisés Maestro-López, Miriam Olombrada, Lucía García-Ortega, Daniel Serrano-González, Javier Lacadena, Mercedes Oñaderra, José G. Gavilanes, Álvaro Martínez-del-Pozo
      Fungal ribotoxins are highly specific extracellular RNases which cleave a single phosphodiester bond at the ribosomal sarcin-ricin loop, inhibiting protein biosynthesis by interfering with elongation factors. Most ribotoxins show high degree of conservation, with similar sizes and amino acid sequence identities above 85%. Only two exceptions are known: Hirsutellin A and anisoplin, produced by the entomopathogenic fungi Hirsutella thompsonii and Metarhizium anisopliae, respectively. Both proteins are similar but smaller than the other known ribotoxins (130 vs 150 amino acids), displaying only about 25% sequence identity with them. They can be considered minimized natural versions of their larger counterparts, best represented by α-sarcin. The conserved α-sarcin active site residue Tyr48 has been replaced by the geometrically equivalent Asp, present in the minimized ribotoxins, to produce and characterize the corresponding mutant. As a control, the inverse anisoplin mutant (D43Y) has been also studied. The results show how the smaller versions of ribotoxins represent an optimum compromise among conformational freedom, stability, specificity, and active-site plasticity which allow these toxic proteins to accommodate the characteristic abilities of ribotoxins into a shorter amino acid sequence and more stable structure of intermediate size between that of other nontoxic fungal RNases and previously known larger ribotoxins.

      PubDate: 2017-03-08T23:12:59Z
      DOI: 10.1016/j.abb.2017.03.002
       
  • NMR-based automated protein structure determination
    • Authors: Julia M. Würz; Sina Kazemi; Elena Schmidt; Anurag Bagaria; Peter Güntert
      Abstract: Publication date: Available online 2 March 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Julia M. Würz, Sina Kazemi, Elena Schmidt, Anurag Bagaria, Peter Güntert
      NMR spectra analysis for protein structure determination can now in many cases be performed by automated computational methods. This overview of the computational methods for NMR protein structure analysis presents recent automated methods for signal identification in multidimensional NMR spectra, sequence-specific resonance assignment, collection of conformational restraints, and structure calculation, as implemented in the CYANA software package. These algorithms are sufficiently reliable and integrated into one software package to enable the fully automated structure determination of proteins starting from NMR spectra without manual interventions or corrections at intermediate steps, with an accuracy of 1–2 Å backbone RMSD in comparison with manually solved reference structures.

      PubDate: 2017-03-02T23:11:53Z
      DOI: 10.1016/j.abb.2017.02.011
       
  • NMR-based Stable Isotope Resolved Metabolomics in systems biochemistry
    • Authors: Andrew N. Lane; Teresa W-M. Fan
      Abstract: Publication date: Available online 2 March 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Andrew N. Lane, Teresa W-M. Fan
      Metabolism is the basic activity of live cells, and monitoring the metabolic state provides a dynamic picture of the cells or tissues, and how they respond to external changes, for in disease or treatment with drugs. NMR is an extremely versatile analytical tool that can be applied to a wide range of biochemical problems. Despite its modest sensitivity its versatility make it an ideal tool for analyzing biochemical dynamics both in vitro and in vivo, especially when coupled with its isotope editing capabilities, from which isotope distributions can be readily determined. These are critical for any analyses of flux in live organisms. This review focuses on the utility of NMR spectroscopy in metabolomics, with an emphasis on NMR applications in stable isotope-enriched tracer research for elucidating biochemical pathways and networks with examples from nucleotide biochemistry. The knowledge gained from this area of research provides a ready link to genomic, epigenomic, transcriptomic, and proteomic information to achieve systems biochemical understanding of living cells and organisms.

      PubDate: 2017-03-02T23:11:53Z
      DOI: 10.1016/j.abb.2017.02.009
       
  • The Emperor's new clothes: Myths and truths of in-cell NMR
    • Authors: Annalisa Pastore; Piero Andrea Temussi
      Abstract: Publication date: Available online 1 March 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Annalisa Pastore, Piero Andrea Temussi
      In-cell NMR is a technique developed to study the structure and dynamical behavior of biological macromolecules in their natural environment, circumventing all isolation and purification steps. In principle, the potentialities of the technique are enormous, not only for the possibility of bypassing all purification steps but, even more importantly, for the wealth of information that can be gained from directly monitoring interactions among biological macromolecules in a natural cell. Here, we review critically the promises, successes and limits of this technique as it stands now. Interestingly, many of the problems of NMR in bacterial cells stem from the artificially high concentration of the protein under study whose overexpression is anyway necessary to select it from the background. This has, as a consequence, that when overexpressed, most globular proteins, do not show an NMR spectrum, limiting the applicability of the technique to intrinsically unfolded or specifically behaving proteins. The outlook for in-cell NMR of eukaryotic cells is more promising and is possibly the most attracting aspect for the future.

      PubDate: 2017-03-02T23:11:53Z
      DOI: 10.1016/j.abb.2017.02.008
       
  • Red/ox states of human protein disulfide isomerase regulates binding
           affinity of 17-Beta-Estradiol
    • Authors: Razieh Karamzadeh; Mohammad Hossein Karimi-Jafari; Ali Akbar Saboury; Ghasem Hosseini-Salekdeh; Ali Akbar Moosavi-Movahedi
      Abstract: Publication date: Available online 28 February 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Razieh Karamzadeh, Mohammad Hossein Karimi-Jafari, Ali Akbar Saboury, Ghasem Hosseini-Salekdeh, Ali Akbar Moosavi-Movahedi
      Human protein disulfide isomerase (hPDI) is a key redox-regulated thiol-containing protein operating as both oxidoreductase and molecular chaperone in the endoplasmic reticulum of cells. hPDI thiol-disulfide interchange reactions lead to the adoption of two distinct red/ox conformations with different substrate preferences. hPDI also displays high binding capacity for some exogenous steroid hormones including 17-Beta-Estradiol (E2) and thus contributes to the regulation of their intracellular concentration, storage and actions. The primary focus of this study is to investigate the impact of E2 binding on functional activity of recombinant hPDI. Then, we examine the effect of E2 binding on structural alteration of hPDI red/ox conformations and its influence on affinity and position of interaction using experimental and computational analysis. Our results revealed that interaction of one E2 per each hPDI molecule leads to the inhibition of hPDI reductase activity and conformational changes in both oxidation states. Mutually, E2-binding position are also redox-regulated with higher affinity in oxidized hPDI compare to the reduced form. The importance of histidine-256 protonation states in distinct binding preferences of E2 were also demonstrated in hPDI red/ox conformations. These findings might pave the way for better understanding of the mechanisms behind the redox-dependent hormone-binding activity of hPDI.

      PubDate: 2017-03-02T23:11:53Z
      DOI: 10.1016/j.abb.2017.02.010
       
  • Targeting thioredoxin reductase by plumbagin contributes to inducing
           apoptosis of HL-60 cells
    • Authors: Junmin Zhang; Shoujiao Peng; Xinming Li; Ruijuan Liu; Xiao Han; Jianguo Fang
      Abstract: Publication date: Available online 27 February 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Junmin Zhang, Shoujiao Peng, Xinming Li, Ruijuan Liu, Xiao Han, Jianguo Fang
      Plumbagin (PLB), a natural naphthoquinone from the traditional folk medicines Plumbago zeylanica, Dionaea muscipula, or Nepenthes gracilis, has been documented possessing a wide variety of pharmacological activities. Although PLB demonstrates anticancer activity in multiple types of malignant cells, the cellular targets of PLB have not been well defined and remained only partially understood. We reported here that PLB selectively inhibits TrxR and elicits reactive oxygen species in human promyelocytic leukemia HL-60 cells, which leads to elevation of GSSG/GSH ratio and decrease of cellular thiol pool. As a consequence, PLB disturbs the cellular redox homeostasis, induces oxidative stress-mediated apoptosis and eventually selectively kills HL-60 cells. Inhibition of TrxR by PLB thus discloses an unprecedented mechanism underlying the anticancer efficacy of PLB, and sheds light in considering the usage of PLB as a promising cancer therapeutic agent.
      Graphical abstract image

      PubDate: 2017-03-02T23:11:53Z
      DOI: 10.1016/j.abb.2017.02.007
       
  • Identification and characterization of a novel starch branching enzyme
           from the picoalgae Ostreococcus tauri
    • Authors: Nicolas Hedin; Julieta Barchiesi Diego Gomez-Casati Alberto Iglesias Miguel Ballicora
      Abstract: Publication date: Available online 21 February 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Nicolas Hedin, Julieta Barchiesi, Diego F. Gomez-Casati, Alberto A. Iglesias, Miguel A. Ballicora, María V. Busi
      Starch branching enzyme is a highly conserved protein from plants to algae. This enzyme participates in starch granule assembly by the addition of α-1,6-glucan branches to the α-1,4-polyglucans. This modification determines the structure of amylopectin thus arranging the final composition of the starch granule. Herein, we describe the function of the Ot01g03030 gene from the picoalgae Ostreococcus tauri. Although in silico analysis suggested that this gene codes for a starch debranching enzyme, our biochemical studies support that this gene encodes a branching enzyme (BE). The resulting 1058 amino acids protein has two in tandem carbohydrate binding domains (CBMs, from the CBM41 and CBM48 families) at the N-terminal (residues 64–403) followed by the C-terminal catalytic domain (residues 426–1058). Analysis of the BE truncated isoforms show that the CBMs bind differentially to whole starch, amylose or amylopectin. Furthermore, both CBMs seem to be essential for BE activity, as no catalytic activity was detected in the truncated enzyme comprising only by the catalytic domain. Our results suggest that the Ot01g03030 gene codifies for a functional BE containing two CBMs from CBM41 and CBM48 families which are critical for enzyme function and regulation.

      PubDate: 2017-02-23T16:50:05Z
       
  • Characterization of Acyl-CoA synthetase isoforms in pancreatic beta cells:
           Gene silencing shows participation of ACSL3 and ACSL4 in insulin secretion
           
    • Authors: Israr-ul H. Ansari; Melissa J. Longacre; Scott W. Stoker; Mindy A. Kendrick; Lucas M. O'Neill; Laura J. Zitur; Luis A. Fernandez; James M. Ntambi; Michael J. MacDonald
      Abstract: Publication date: Available online 11 February 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Israr-ul H. Ansari, Melissa J. Longacre, Scott W. Stoker, Mindy A. Kendrick, Lucas M. O'Neill, Laura J. Zitur, Luis A. Fernandez, James M. Ntambi, Michael J. MacDonald
      Long-chain acyl-CoA synthetases (ACSLs) convert fatty acids to fatty acyl-CoAs to regulate various physiologic processes. We characterized the ACSL isoforms in a cell line of homogeneous rat beta cells (INS-1832/13 cells) and human pancreatic islets. ACSL4 and ACSL3 proteins were present in the beta cells and human and rat pancreatic islets and concentrated in insulin secretory granules and less in mitochondria and negligible in other intracellular organelles. ACSL1 and ACSL6 proteins were not seen in INS-1832/13 cells or pancreatic islets. ACSL5 protein was seen only in INS-1832/13 cells. With shRNA-mediated gene silencing we developed stable ACSL knockdown cell lines from INS-1832/13 cells. Glucose-stimulated insulin release was inhibited ∼50% with ACSL4 and ACSL3 knockdown and unaffected in cell lines with knockdown of ACSL5, ACLS6 and ACSL1. Lentivirus shRNA-mediated gene silencing of ACSL4 and ACSL3 in human pancreatic islets inhibited glucose-stimulated insulin release. ACSL4 and ACSL3 knockdown cells showed inhibition of ACSL enzyme activity more with arachidonate than with palmitate as a substrate, consistent with their preference for unsaturated fatty acids as substrates. ACSL4 knockdown changed the patterns of fatty acids in phosphatidylserines and phosphatidylethanolamines. The results show the involvement of ACLS4 and ACLS3 in insulin secretion.

      PubDate: 2017-02-11T11:33:55Z
      DOI: 10.1016/j.abb.2017.02.001
       
  • Mechanism of inhibition of botulinum neurotoxin type A light chain by two
           quinolinol compounds
    • Authors: Yacoba V.T. Minnow; Ronald Goldberg; Sreedhar R. Tummalapalli; David P. Rotella; Nina M. Goodey
      Abstract: Publication date: Available online 28 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yacoba V.T. Minnow, Ronald Goldberg, Sreedhar R. Tummalapalli, David P. Rotella, Nina M. Goodey
      Quinolinol-based compounds are a promising starting point for discovery of effective inhibitors of the clostridial neurotoxin, botulinum neurotoxin type A light chain (BoNT/A LC). Insights into the mechanism of inhibition by quinolinol compounds facilitate interpretation of docking data and inhibitor optimization. In this study, a fluorogenic substrate of BoNT/A, SNAPtide, was used to study the mechanism by which two new quinolinol compounds, MSU58 and MSU84, with IC50 values of 3.3 μM and 5.8 μM, respectively, inhibit BoNT/A LC. Kinetic studies and model discrimination analysis showed both compounds to be competitive inhibitors of BoNT/A LC with inhibition constants (KI) 3.2 μM and 6.2 μM for MSU58 and MSU84, respectively. These data indicate that the inhibitors bind in the BoNT/A LC active site and that inhibitor binding is mutually exclusive with the binding of the substrate. This is the first study to report the competitive inhibition of BoNT/A LC by quinolinol compounds. These data help define the inhibitor binding pocket and, along with structure activity relationship studies, provide immediate direction for further compound synthesis.
      Graphical abstract image

      PubDate: 2017-01-29T17:41:45Z
      DOI: 10.1016/j.abb.2017.01.006
       
  • 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
      Abstract: Publication date: Available online 28 January 2017
      Source:Archives of Biochemistry and Biophysics
      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: 2017-01-29T17:41:45Z
      DOI: 10.1016/j.abb.2017.01.013
       
  • Oligomerization affects the kinetics and thermodynamics of the interaction
           of a Bowman-Birk inhibitor with proteases
    • Authors: G.D. Brand; D.A.T. Pires; J.R. Furtado; A. Cooper; S.M. Freitas; C. Bloch
      Abstract: Publication date: Available online 26 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): G.D. Brand, D.A.T. Pires, J.R. Furtado, A. Cooper, S.M. Freitas, C. Bloch
      The black-eyed pea trypsin/chymotrypsin inhibitor (BTCI) forms concentration dependent homomultimers, as previously demonstrated by Light scattering and Atomic Force Microscopy. Considering that these self-aggregates might influence their binding to cognate enzymes, we investigated the interaction of BTCI at picomolar concentrations using surface immobilized Chymotrypsin (α-CT) and Trypsin (T) by Surface Plasmon Resonance. Our results indicate that BTCI has subnanomolar affinity to both immobilized enzymes, which is approximately two orders of magnitude higher than previously reported. Moreover, we probed the influence of temperature on protein binding equilibria in order to investigate their interaction energetics. While the BTCI/T interaction concurs with the canonical entropy-driven mechanism described for BBI interactions with serine proteinases, the BTCI/α-CT interaction does not. Our measurements indicate that bimolecular BTCI/α-CT complexes form with a negative enthalpy change and a moderate entropic increase. Direct calorimetric evaluation is in accord with the van't Hoff approximation obtained by SPR. We demonstrate that as protein concentrations increase to the micromolar range, secondary endothermic events become prevalent and affect both the kinetics and thermodynamics of protein associations. Our study reinforces that BBI interactions with serine proteinases should be studied in dilute solutions to abridge often neglected secondary interactions.

      PubDate: 2017-01-29T17:41:45Z
      DOI: 10.1016/j.abb.2017.01.009
       
  • Redox sensing molecular mechanism of an iron metabolism regulatory protein
           FBXL5
    • Authors: Yaozhu Wei; Hong Yuan; Pengbiao Xu; Xiangshi Tan
      Abstract: Publication date: Available online 25 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yaozhu Wei, Hong Yuan, Pengbiao Xu, Xiangshi Tan
      FBXL5 is a subunit of the SCFFBXL5 ubiquitin ligase complex that targets the proteasomal degradation of iron regulatory protein IRP2, which is an important regulator in iron metabolism. The degradation of FBXL5 itself is regulated in an iron- and oxygen-responsive manner through its diiron center containing Hr-like domain. Although the crystal structure of the Hr-like domain of FBXL5 and its degradation based on iron/oxygen sensing has been reported, the redox sensing molecular mechanism is still not clear. Herein the redox properties of FBXL5 were investigated via EPR, direct electrochemistry, SRCD, fluorescence emission spectroscopy, and redox kinetics. The results indicated that the conformation and function of FBXL5 are tuned by the redox states of the diiron center. The redox reactions of the diiron center are accompanied with conformational changes and iron release, which are associated with FBXL5 stability and degradation. These results provide insights into the redox sensing mechanism by which FBXL5 can serve as an iron metabolism regulator within mammalian cells.
      Graphical abstract image

      PubDate: 2017-01-29T17:41:45Z
      DOI: 10.1016/j.abb.2016.12.002
       
  • In vitro actin motility velocity varies linearly with the number of myosin
           impellers
    • Authors: Y. Wang; T.P. Burghardt
      Abstract: Publication date: Available online 25 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Y. Wang, T.P. Burghardt
      Cardiac myosin is the motor powering the heart. It moves actin with 3 step-size varieties generated by torque from the myosin heavy chain lever-arm rotation under the influence of myosin essential light chain whose N-terminal extension binds actin. Proposed mechanisms adapting myosin mechanochemical characteristics on the fly sometimes involve modulation of step-size selection probability via motor strain sensitivity. Strain following the power stroke, hypothetically imposed by the finite actin detachment rate 1/ton, is shown to have no effect on unloaded velocity when multiple myosins are simultaneously strongly actin bound in an in vitro motility assay. Actin filaments slide ∼2 native step-sizes while more than 1 myosin strongly binds actin probably ruling out an actin detachment limited model for imposing strain. It suggests that single myosin estimates for ton are too large, not applicable to the ensemble situation, or both. Parallel motility data quantitation involving instantaneous particle velocities (frame velocity) and actin filament track averaged velocities (track velocity) give an estimate of the random walk step-size, δ. Comparing δ for slow and fast motility components suggests the higher speed component has cardiac myosin upshifting to longer steps. Variable step-size characteristics imply cardiac myosin maintains a velocity dynamic range not involving strain.
      Graphical abstract image

      PubDate: 2017-01-29T17:41:45Z
      DOI: 10.1016/j.abb.2017.01.012
       
  • Specificity and mechanism of mandelamide hydrolase catalysis
    • Authors: S.A. Adediran; Pan-Fen Wang; Abbas G. Shilabin; Charles A. Baron; Michael J. McLeish; R.F.Pratt
      Abstract: Publication date: Available online 24 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): S.A. Adediran, Pan-Fen Wang, Abbas G. Shilabin, Charles A. Baron, Michael J. McLeish, R.F.Pratt
      The best-studied amidase signature (AS) enzyme is probably fatty acid amide hydrolase (FAAH). Closely related to FAAH is mandelamide hydrolase (MAH), whose substrate specificity and mechanism of catalysis are described in this paper. First, we developed a convenient chromogenic substrate, 4-nitrophenylacetamide, for MAH. The lack of reactivity of MAH with the corresponding ethyl ester confirmed the very limited size of the MAH leaving group site. The reactivity of MAH with 4-nitrophenyl acetate and methyl 4-nitrophenyl carbonate, therefore, suggested formation of an “inverse” acyl-enzyme where the small acyl-group occupies the normal leaving group site. We have interpreted the specificity of MAH for phenylacetamide substrates and small leaving groups in terms of its active site structure, using a homology model based on a FAAH crystal structure. The relevant structural elements were compared with those of FAAH. Phenylmethylboronic acid is a potent inhibitor of MAH (Ki = 27 nM), presumably because it forms a transition state analogue structure with the enzyme. O-Acyl hydroxamates were not irreversible inactivators of MAH but some were found to be transient inhibitors.
      Graphical abstract image

      PubDate: 2017-01-29T17:41:45Z
      DOI: 10.1016/j.abb.2017.01.010
       
  • The role of sulfenic acids in cellular redox signaling: Reconciling
           chemical kinetics and molecular detection strategies
    • Authors: David E. Heppner; Yvonne M.W. Janssen-Heininger; Albert van der Vliet
      Abstract: Publication date: Available online 23 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): David E. Heppner, Yvonne M.W. Janssen-Heininger, Albert van der Vliet
      The reversible oxidation of protein cysteine residues is well recognized as an important regulatory mechanism in redox-dependent cell signaling. Cysteine oxidation is diverse in nature and involves various post-translational modifications (sulfenic acids, disulfides, etc.) and the specific functional or structural impact of these specific oxidative events is still poorly understood. The proximal product of protein cysteine oxidation by biological reactive oxygen species (ROS) is sulfenic acid (Cys-SOH), and experimental evidence is accruing for the formation of Cys-SOH as intermediate in protein cysteine oxidation in various biological settings. However, the plausibility of protein Cys-SH oxidation by ROS has often been put in question because of slow reaction kinetics compared to more favorable reactions with abundant thiol-based reductants such as peroxiredoxins (Prx) or glutathione (GSH). This commentary aims to address this controversy by highlighting the unique physical properties in cells that may restrict ROS diffusion and allow otherwise less favorable cysteine oxidation of proteins. Some limitations of analytical tools to assess Cys-SOH are also discussed. We conclude that formation of Cys-SOH in biological systems cannot always be predicted based on kinetic analyses in homogenous solution, and may be facilitated by unique structural and physical properties of Cys-containing proteins within e.g. signaling complexes.

      PubDate: 2017-01-29T17:41:45Z
      DOI: 10.1016/j.abb.2017.01.008
       
  • Metformin and low dose radiation modulates cisplatin-induced oxidative
           injury in rat via PPAR-γ and MAPK pathways
    • Authors: Heba H. Mansour; Shereen M. El kiki; Shereen M. Galal
      Abstract: Publication date: Available online 16 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Heba H. Mansour, Shereen M. El kiki, Shereen M. Galal
      Cisplatin (CIS) is a chemotherapeutic agent used for therapy of many tumors and has been limited by its toxicity. The aim of this study was to investigate the role of Peroxisome proliferator–activated receptor-gamma (PPAR-γ), mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B(NFkB) in the pathogenesis of hepatic damage induced by CIS, and investigated the modulatory effect of metformin (MET) and/or low dose gamma radiation (LDR) on CIS-induced hepatotoxicity in rats. CIS(7.5 mg/kg, i.p.) hepatotoxicity was evidenced by alteration of serum hepatic indices (ALT and AST) accompanied with decreased hepatic PPAR-γ, superoxide dismutase (SOD) activities and reduced glutathione (GSH) content, whereas the levels of malondialdehyde (MDA), total nitrate/nitrite (NOx) and NFkB significantly increased as well as MAPK activity compared with the control, MET and LDR groups. Furthermore, CIS induces apoptosis as indicated by an elevation of hepatic caspase-3. Treatment with MET (150 mg/kg, orally for 14 days) and/or LDR (0.5 Gy), prior to CIS alleviates CIS-induced hepatic damage by mitigating oxidative/ nitrosative stress and PPAR-γ activity reduction, hepatic caspase-3 elevation, and inhibition of NFκB, and MAPK activity levels. Conclusions: Modulation of PPAR-γ, MAPK and NFkB might contribute to amelioration of CIS-induced hepatic toxicity.
      Graphical abstract image

      PubDate: 2017-01-22T17:25:09Z
      DOI: 10.1016/j.abb.2017.01.005
       
  • CFTR impairment upregulates c-Src activity through IL-1β autocrine
           signaling
    • Authors: María Macarena Massip-Copiz; Mariángeles Clauzure; Ángel Gabriel Valdivieso; Tomás Antonio Santa-Coloma
      Abstract: Publication date: Available online 11 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): María Macarena Massip-Copiz, Mariángeles Clauzure, Ángel Gabriel Valdivieso, Tomás Antonio Santa-Coloma
      Cystic Fibrosis (CF) is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Previously, we found several genes showing a differential expression in CFDE cells (epithelial cells derived from a CF patient). One corresponded to c-Src; its expression and activity was found increased in CFDE cells, acting as a signaling molecule between the CFTR activity and MUC1 overexpression. Here we report that bronchial IB3-1 cells (CF cells) also showed increased c-Src activity compared to ‘CFTR-corrected’ S9 cells. In addition, three different Caco-2 cell lines, each stably transfected with a different CFTR-specific shRNAs, displayed increased c-Src activity. The IL-1β receptor antagonist IL1RN reduced the c-Src activity of Caco-2/pRS26 cells (expressing a CFTR-specific shRNA). In addition, increased mitochondrial and cellular ROS levels were detected in Caco-2/pRS26 cells. ROS levels were partially reduced by incubation with PP2 (c-Src inhibitor) or IL1RN, and further reduced by using the NOX1/4 inhibitor GKT137831. Thus, IL-1β→c-Src and IL-1β→NOX signaling pathways appear to be responsible for the production of cellular and mitochondrial ROS in CFTR-KD cells. In conclusion, IL-1β constitutes a new step in the CFTR signaling pathway, located upstream of c-Src, which is stimulated in cells with impaired CFTR activity.

      PubDate: 2017-01-15T17:06:57Z
      DOI: 10.1016/j.abb.2017.01.003
       
  • Introduction for the Special Issue on the Chemistry of Redox Signaling
    • Authors: Henry Jay Forman; Willem H. Koppenol
      Abstract: Publication date: Available online 11 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Henry Jay Forman, Willem H. Koppenol


      PubDate: 2017-01-15T17:06:57Z
      DOI: 10.1016/j.abb.2017.01.004
       
  • Altered myocyte contractility and calcium homeostasis in alpha-myosin
           heavy chain point mutations linked to familial dilated cardiomyopathy
    • Authors: Matthew Klos; Lakshmi Mundada; Indroneal Banerjee; Sherry Morgenstern; Stephanie Myers; Michael Leone; Mark Kleid; Todd Herron; Eric Devaney
      Abstract: Publication date: Available online 11 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Matthew Klos, Lakshmi Mundada, Indroneal Banerjee, Sherry Morgenstern, Stephanie Myers, Michael Leone, Mark Kleid, Todd Herron, Eric Devaney
      Mutations in the human cardiac motor protein beta-myosin heavy chain (βMHC) have been long recognized as a cause of familial hypertrophic cardiomyopathy. Recently, mutations (P830L and A1004S) in the less abundant but faster isoform alpha-myosin heavy chain (αMHC) have been linked to dilated cardiomyopathy (DCM). In this study, we sought to determine the cellular contractile phenotype associated with these point mutations. Ventricular myocytes were isolated from 2 month male Sprague Dawley rats. Cells were cultured in M199 media and infected with recombinant adenovirus containing the P830L or the A1004S mutant human αMHC at a MOI of 500 for 18 h. Uninfected cells (UI), human βMHC (MOI 500, 18 h), and human αMHC (MOI 500, 18 h) were used as controls. Cells were loaded with fura-2 (1 μM, 15 min) after 48 h. Sarcomere shortening and calcium transients were recorded in CO2 buffered M199 media (36°±1 C) with and without 10 nM isoproterenol (Iso). The A1004S mutation resulted in decreased peak sarcomere shortening while P830L demonstrated near normal shortening kinetics at baseline. In the presence of Iso, the A1004S sarcomere shortening was identical to the βMHC shortening while the P830L was identical to the αMHC control. All experimental groups had identical calcium transients. Despite a shared association with DCM, the P830L and A1004S αMHC mutations alter myocyte contractility in completely different ways while at the same preserving peak intracellular calcium.

      PubDate: 2017-01-15T17:06:57Z
      DOI: 10.1016/j.abb.2016.12.007
       
  • The key residue within the second extracellular loop of human EP3 involved
           in selectively turning down PGE2-and retaining PGE1-mediated signaling in
           live cells
    • Authors: Hironari Akasaka; Natasha Thaliachery; Xianghai Zheng; Marissa Blumenthal; Sameer Nikhar; Emma E. Murdoch; Qinglan Ling; Ke-He Ruan
      Abstract: Publication date: Available online 5 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Hironari Akasaka, Natasha Thaliachery, Xianghai Zheng, Marissa Blumenthal, Sameer Nikhar, Emma E. Murdoch, Qinglan Ling, Ke-He Ruan
      Key residues and binding mechanisms of PGE1 and PGE2 on prostanoid receptors are poorly understood due to the lack of X-ray structures for the receptors. We constructed a human EP3 (hEP3) model through integrative homology modeling using the X-ray structure of the β2-adrenergic receptor transmembrane domain and NMR structures of the thromboxane A2 receptor extracellular loops. PGE1 and PGE2 docking into the hEP3 model showed differing configurations within the extracellular ligand recognition site. While PGE2 could form possible binding contact with S211, PGE1 is unable to form similar contacts. Therefore, S211 could be the critical residue for PGE2 recognition, but is not a significant for PGE1. This prediction was confirmed using HEK293 cells transfected with S211L cDNA. The S211L cells lost PGE2 binding and signaling. Interestingly, the S211L cells retained PGE1-mediated signaling. It indicates that S211 within the second extracellular loop is a key residue involved in turning down PGE2 signaling. Our study provided information that S211L within EP3 is the key residue to distinguish PGE1 and PGE2 binding to mediate diverse biological functions at the initial recognition step. The S211L mutant could be used as a model for studying the binding mechanism and signaling pathway specifically mediated by PGE1.
      Graphical abstract image

      PubDate: 2017-01-07T16:29:04Z
      DOI: 10.1016/j.abb.2016.12.001
       
  • Vitamin D supplementation inhibits oxidative stress and upregulate
           SIRT1/AMPK/GLUT4 cascade in high glucose-treated 3T3L1 adipocytes and in
           adipose tissue of high fat diet-fed diabetic mice
    • Authors: Prasenjit Manna; Arunkumar E. Achari; Sushil K. Jain
      Abstract: Publication date: Available online 4 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Prasenjit Manna, Arunkumar E. Achari, Sushil K. Jain
      This study examined the hypothesis that vitamin-D prevents oxidative stress and upregulates glucose metabolism via activating insulin-independent signaling molecules in 3T3-L1 adipocytes and in high fat diet (HFD)-fed mice. To investigate the mechanism 3T3L1 adipocytes were treated with high glucose (HG, 25 mM) and 1,25(OH)2D3 (1,25-dihydroxyvitamin D3) (0–50 nM). Results showed that 1,25(OH)2D3 supplementation decreased NOX4 expression, ROS production, NF-κB phosphorylation, and increased the expression of Nrf2 and Trx in HG-treated cells. 1,25(OH)2D3 supplementation upregulated SIRT1 expression and AMPK phosphorylation and stimulated the IRS1/PI3K/PIP3/AKT/PKCζ signaling cascade, GLUT4 expression, and glucose uptake in HG-treated adipocytes. The effect of 1,25(OH)2D3 on the phosphorylation of both AMPK and IRS1, GLUT4 expression, and glucose uptake was significantly inhibited in SIRT1-knockdown adipocytes. This suggests the role of insulin-independent signaling molecules (SIRT1, AMPK) in mediating the effect of 1,25(OH)2D3 on the signaling cascade of glucose uptake. In addition, cholecalciferol supplementation significantly upregulated pAMPK, SIRT-1 and GLUT-4 levels in adipose tissue of mice fed with HFD. This study demonstrates a novel molecular mechanism by which vitamin-D can prevent oxidative stress and upregulates glucose uptake via SIRT1/AMPK/IRS1/GLUT4 cascade in HG-treated adipocytes and in adipose tissue of HFD diabetic mice.

      PubDate: 2017-01-07T16:29:04Z
      DOI: 10.1016/j.abb.2017.01.002
       
  • Cytokine IL-10, activators of PI3-kinase, agonists of α-2 adrenoreceptor
           and antioxidants prevent ischemia-induced cell death in rat hippocampal
           cultures
    • Authors: Egor A. Turovsky; Maria V. Turovskaya; Sergei G. Gaidin; Valery P. Zinchenko
      Abstract: Publication date: Available online 4 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Egor A. Turovsky, Maria V. Turovskaya, Sergei G. Gaidin, Valery P. Zinchenko
      In the present work we compared the protective effect of anti-inflammatory cytokine IL-10 with the action of a PI3-kinase selective activator 740Y-P, selective agonists of alpha-2 adrenoreceptor, guanfacine and UK-14,304, and compounds having antioxidant effect: recombinant human peroxiredoxin 6 and B27, in hippocampal cell culture during OGD (ischemia-like conditions). It has been shown that the response of cells to OGD in the control includes two phases. The first phase was accompanied by an increase in the frequency of spontaneous synchronous Ca2+-oscillations (SSCO) in neurons and Ca2+-pulse in astrocytes. Spontaneous Ca2+ events in astrocytes during ischemia in control experiments disappeared. The second phase started after a few minutes of OGD and looked like a sharp/avalanche, global synchronic (within 20 s) increase in [Ca2+]i in many cells. Within 1 h after OGD, a mass death of cells, primarily astrocytes, was observed. To study the protective action of the compounds, cells were incubated in the presence of the neuroprotective agents for 10–40 min or 24 h before ischemia. All the neuroprotective agents delayed a global [Ca2+]i increase during OGD or completely inhibited this process and increased cell survival.

      PubDate: 2017-01-07T16:29:04Z
      DOI: 10.1016/j.abb.2017.01.001
       
  • The long non-coding RNA NEAT1 interacted with miR-101 modulates breast
           cancer growth by targeting EZH2
    • Authors: Ke Qian; Gao Liu; Zhonghua Tang; Yibo Hu; Yu Fang; Zonglin Chen; Xundi Xu
      Abstract: Publication date: Available online 26 December 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Ke Qian, Gao Liu, Zhonghua Tang, Yibo Hu, Yu Fang, Zonglin Chen, Xundi Xu
      Nuclear enriched abundant transcript 1 (NEAT1), an important cancer-associated long non-coding RNA (lncRNA), contributes to the development and progression of several cancers. An increased expression of NEAT1 was observed in cancers including bladder cancer, lung cancer and breast cancer (BC). However, the exact effect of NEAT1 in BC progression and the underlying molecular mechanisms are still unknown up to now. Here, we investigated the detailed role of NEAT1 in human BC cell lines and clinical tumor samples in order to validate the function of this molecule. In our research, lncRNA-NEAT1 was specifically upregulated in BC cell lines and promoted BC cell growth through targeting miR-101. Knockdown of NEAT1 inhibited the proliferation and DNA synthesis of human BC cell in vitro. In addition, the regulation of EZH2 by miR-101 was required in NEAT1 induced BC cell growth. These findings indicated that NEAT1 might suppress the tumor growth via miR-101 dependent EZH2 regulation. Taken together, our data indicated that NEAT1 might be an oncogenic lncRNA that promoted proliferation of BC and could be regarded as a therapeutic target in human BC.

      PubDate: 2016-12-29T15:56:49Z
      DOI: 10.1016/j.abb.2016.12.011
       
  • Peroxiredoxin 6 in the repair of peroxidized cell membranes and cell
           signaling
    • Authors: Aron B. Fisher
      Abstract: Publication date: Available online 6 December 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Aron B. Fisher
      Peroxiredoxin 6 represents a widely distributed group of peroxiredoxins that contain a single conserved cysteine in the protein monomer (1-cys Prdx). The cys when oxidized to the sulfenic form is reduced with glutathione (GSH) catalyzed by the π isoform of GSH-S-transferase. Three enzymatic activities of the protein have been described:1) peroxidase with H2O2, short chain hydroperoxides and phospholipid hydroperoxides as substrates; 2) phospholipase A2 (PLA2); and 3) lysophosphatidylcholine acyl transferase (LPCAT). These activities have important physiological roles in antioxidant defense, turnover of cellular phospholipids, and the generation of superoxide anion via initiation of the signaling cascade for activation of NADPH oxidase (type 2). The ability of Prdx6 to reduce peroxidized cell membrane phospholipids (peroxidase activity) and also to replace the oxidized sn-2 fatty acyl group through hydrolysis/reacylation (PLA2 and LPCAT activities) provides a complete system for the repair of peroxidized cell membranes.

      PubDate: 2016-12-08T01:10:59Z
      DOI: 10.1016/j.abb.2016.12.003
       
 
 
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