Methionine sulfoxide reductase: Chemistry,substrate binding,recycling process and oxidase activity |
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| Affiliation: | 1. Department of Experimental Neurodegeneration, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen 37073, Germany;2. Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Göttingen, Göttingen, Germany;3. Department for Functional Genomics, Center for Translational and Clinical Research, University Hospital Center Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia;4. Institute of Medical Genetics and Applied Genomics, Faculty of Medicine, University of Tübingen, Tübingen 72076, Germany;5. Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany;6. Department of Neurology, University Medical Center Göttingen, Göttingen, Germany;7. CEDOC – Chronic Diseases Research Center, Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisboa, Portugal;8. Max Planck Institute for Experimental Medicine, Göttingen 37075, Germany;9. Institute of Neuroscience, The Medical School, Newcastle University, Framlington Place, Newcastle NE2 4HH, UK |
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| Abstract: | Three classes of methionine sulfoxide reductases are known: MsrA and MsrB which are implicated stereo-selectively in the repair of protein oxidized on their methionine residues; and fRMsr, discovered more recently, which binds and reduces selectively free L-Met-R-O. It is now well established that the chemical mechanism of the reductase step passes through formation of a sulfenic acid intermediate. The oxidized catalytic cysteine can then be recycled by either Trx when a recycling cysteine is operative or a reductant like glutathione in the absence of recycling cysteine which is the case for 30% of the MsrBs. Recently, it was shown that a subclass of MsrAs with two recycling cysteines displays an oxidase activity. This reverse activity needs the accumulation of the sulfenic acid intermediate. The present review focuses on recent insights into the catalytic mechanism of action of the Msrs based on kinetic studies, theoretical chemistry investigations and new structural data. Major attention is placed on how the sulfenic acid intermediate can be formed and the oxidized catalytic cysteine returns back to its reduced form. |
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| Keywords: | Methionine sulfoxide reductase Reductase process Recycling process Oxidase activity Three-dimensional structures |
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