View source for 6qa0


==MSRB3 - AA 1-137==
<StructureSection load='6qa0' size='340' side='right'caption='[[6qa0]], [[Resolution|resolution]] 1.71&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.709&#8491;</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='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>
</table>
== Disease ==
[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 ==
[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;">
== 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<ref>PMID:32517586</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6qa0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fass D]]
[[Category: Javitt G]]