6tr8: Difference between revisions
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==Corynebacterium diphtheriae methionine sulfoxide reductase B (MsrB) solution structure - reduced form== | |||
<StructureSection load='6tr8' size='340' side='right'caption='[[6tr8]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6tr8]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TR8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6TR8 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptide-methionine_(R)-S-oxide_reductase Peptide-methionine (R)-S-oxide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.4.12 1.8.4.12] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6tr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tr8 OCA], [http://pdbe.org/6tr8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tr8 RCSB], [http://www.ebi.ac.uk/pdbsum/6tr8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tr8 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Corynebacterium diphtheriae is a human pathogen that causes diphtheria. In response to immune system-induced oxidative stress, C. diphtheriae expresses antioxidant enzymes, among which are methionine sulfoxide reductase (Msr) enzymes, which are critical for bacterial survival in the face of oxidative stress. Although some aspects of the catalytic mechanism of the Msr enzymes have been reported, several details still await full elucidation. Here, we solved the solution structure of C. diphtheriae MsrB (Cd-MsrB) and unraveled its catalytic and oxidation-protection mechanisms. Cd-MsrB catalyzes methionine sulfoxide reduction involving three redox-active cysteines. Using NMR heteronuclear single-quantum coherence (HSQC) spectra, kinetics, biochemical assays, and MS analyses, we show that the conserved nucleophilic residue Cys122 is S-sulfenylated after substrate reduction, which is then resolved by a conserved cysteine, Cys66, or by the non-conserved residue Cys127. We noted that the overall structural changes during the disulfide cascade expose the Cys122-Cys66 disulfide to recycling through thioredoxin (Trx). In the presence of hydrogen peroxide, Cd-MsrB formed reversible intra- and intermolecular disulfides without losing its Cys-coordinated Zn(2+), and only the non-conserved Cys127 reacted with the low-molecular-weight (LMW) thiol mycothiol, protecting it from overoxidation. In summary, our structure-function analyses reveal critical details of the Cd-MsrB catalytic mechanism, including a major structural rearrangement that primes the Cys122-Cys66 disulfide for Trx reduction and a reversible protection against excessive oxidation of the catalytic cysteines in Cd-MsrB through intra- and intermolecular disulfide formation and S-mycothiolation. | |||
Methionine sulfoxide reductase B from Corynebacterium diphtheriae catalyzes sulfoxide reduction via an intramolecular disulfide cascade.,Tossounian MA, Khanh Truong AC, Buts L, Wahni K, Mourenza A, Leermakers M, Vertommen D, Mateos LM, Volkov AN, Messens J J Biol Chem. 2020 Jan 28. pii: RA119.012438. doi: 10.1074/jbc.RA119.012438. PMID:31992594<ref>PMID:31992594</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6tr8" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Buts, L]] | [[Category: Buts, L]] | ||
[[Category: Messens, J]] | [[Category: Messens, J]] | ||
[[Category: Tossounian, M A]] | |||
[[Category: Volkov, A N]] | |||
[[Category: Catalytic cysteine]] | |||
[[Category: Methionine sulfoxide reductase]] | |||
[[Category: Oxidoreductase]] | |||
[[Category: Reduced structure]] | |||
[[Category: Zinc-coordination]] | |||