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| | <StructureSection load='6qa0' size='340' side='right'caption='[[6qa0]], [[Resolution|resolution]] 1.71Å' scene=''> | | <StructureSection load='6qa0' size='340' side='right'caption='[[6qa0]], [[Resolution|resolution]] 1.71Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6qa0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QA0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QA0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6qa0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QA0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QA0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.709Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAF:S-DIMETHYLARSINOYL-CYSTEINE'>CAF</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAF:S-DIMETHYLARSINOYL-CYSTEINE'>CAF</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MSRB3, UNQ1965/PRO4487 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6qa0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qa0 OCA], [https://pdbe.org/6qa0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qa0 RCSB], [https://www.ebi.ac.uk/pdbsum/6qa0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qa0 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6qa0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qa0 OCA], [http://pdbe.org/6qa0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qa0 RCSB], [http://www.ebi.ac.uk/pdbsum/6qa0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qa0 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/MSRB3_HUMAN MSRB3_HUMAN]] Autosomal recessive non-syndromic sensorineural deafness type DFNB. The disease is caused by mutations affecting the gene represented in this entry. A nonsense mutation affecting exclusively mitochondrial isoform 2 is sufficient to produce hearing loss. | + | [https://www.uniprot.org/uniprot/MSRB3_HUMAN MSRB3_HUMAN] Autosomal recessive non-syndromic sensorineural deafness type DFNB. The disease is caused by mutations affecting the gene represented in this entry. A nonsense mutation affecting exclusively mitochondrial isoform 2 is sufficient to produce hearing loss. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MSRB3_HUMAN MSRB3_HUMAN]] Catalyzes the reduction of free and protein-bound methionine sulfoxide to methionine. Isoform 2 is essential for hearing.<ref>PMID:14699060</ref> <ref>PMID:21185009</ref> | + | [https://www.uniprot.org/uniprot/MSRB3_HUMAN MSRB3_HUMAN] Catalyzes the reduction of free and protein-bound methionine sulfoxide to methionine. Isoform 2 is essential for hearing.<ref>PMID:14699060</ref> <ref>PMID:21185009</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fass, D]] | + | [[Category: Fass D]] |
| - | [[Category: Javitt, G]] | + | [[Category: Javitt G]] |
| - | [[Category: Enzyme]]
| + | |
| - | [[Category: Methionine sulfoxide]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Disease
MSRB3_HUMAN Autosomal recessive non-syndromic sensorineural deafness type DFNB. The disease is caused by mutations affecting the gene represented in this entry. A nonsense mutation affecting exclusively mitochondrial isoform 2 is sufficient to produce hearing loss.
Function
MSRB3_HUMAN Catalyzes the reduction of free and protein-bound methionine sulfoxide to methionine. Isoform 2 is essential for hearing.[1] [2]
Publication Abstract from PubMed
INTRODUCTION: The post-translational oxidation of methionine to methionine sulfoxide is a reversible process, enabling repair of oxidative damage to proteins and the use of sulfoxidation as a regulatory switch. Methionine sulfoxide reductases catalyze the stereospecific reduction of methionine sulfoxide. One of the mammalian methionine sulfoxide reductases, MsrB3, has a signal sequence for entry into the endoplasmic reticulum (ER). In the ER, MsrB3 is expected to encounter a distinct redox environment compared to its paralogs in the cytosol, nucleus, and mitochondria. AIMS: We sought to determine the location and arrangement of MsrB3 redox-active cysteines, which may couple MsrB3 activity to other redox events in the ER. RESULTS: We determined the human MsrB3 structure using X-ray crystallography. The structure revealed that a disulfide bond near the protein amino terminus is distant in space from the active site. Nevertheless, biochemical assays showed that these amino-terminal cysteines are oxidized by the MsrB3 active site after its reaction with methionine sulfoxide. INNOVATION: This study reveals a mechanism to shuttle oxidizing equivalents from the primary MsrB3 active site toward the enzyme surface, where they would be available for further dithiol-disulfide exchange reactions. CONCLUSION: Conformational changes must occur during the MsrB3 catalytic cycle to transfer oxidizing equivalents from the active site to the amino-terminal redox-active disulfide. The accessibility of this exposed disulfide may help couple MsrB3 activity to other dithiol/disulfide redox events in the secretory pathway.
Structure and Electron-transfer Pathway of the Human Methionine Sulfoxide Reductase MsrB3.,Javitt G, Cao Z, Resnick E, Gabizon R, Bulleid N, Fass D Antioxid Redox Signal. 2020 Jun 10. doi: 10.1089/ars.2020.8037. PMID:32517586[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kim HY, Gladyshev VN. Methionine sulfoxide reduction in mammals: characterization of methionine-R-sulfoxide reductases. Mol Biol Cell. 2004 Mar;15(3):1055-64. Epub 2003 Dec 29. PMID:14699060 doi:http://dx.doi.org/10.1091/mbc.E03-08-0629
- ↑ Ahmed ZM, Yousaf R, Lee BC, Khan SN, Lee S, Lee K, Husnain T, Rehman AU, Bonneux S, Ansar M, Ahmad W, Leal SM, Gladyshev VN, Belyantseva IA, Van Camp G, Riazuddin S, Friedman TB, Riazuddin S. Functional null mutations of MSRB3 encoding methionine sulfoxide reductase are associated with human deafness DFNB74. Am J Hum Genet. 2011 Jan 7;88(1):19-29. doi: 10.1016/j.ajhg.2010.11.010. Epub, 2010 Dec 23. PMID:21185009 doi:http://dx.doi.org/10.1016/j.ajhg.2010.11.010
- ↑ Javitt G, Cao Z, Resnick E, Gabizon R, Bulleid N, Fass D. Structure and Electron-transfer Pathway of the Human Methionine Sulfoxide Reductase MsrB3. Antioxid Redox Signal. 2020 Jun 10. doi: 10.1089/ars.2020.8037. PMID:32517586 doi:http://dx.doi.org/10.1089/ars.2020.8037
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