6tr8 | pdb_00006tr8

Corynebacterium diphtheriae methionine sulfoxide reductase B (MsrB) solution structure - reduced form

spinqualitylabelsall models 6tr8, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6tr8 is a 1 chain structure with sequence from "bacillus_diphtheriae"_kruse_in_flugge_1886 "bacillus diphtheriae" kruse in flugge 1886. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZN Gene: msrB, B11Q_01469, B1A51_07985, BT093_04380 ("Bacillus diphtheriae" Kruse in Flugge 1886) Activity: Peptide-methionine (R)-S-oxide reductase, with EC number 1.8.4.12 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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