<p>Peptide methionine sulphoxide reductase (Msr) reverses the inactivation of many proteins due to the oxidation of critical methionine residues by reducing methionine sulphoxide, Met(O), to methionine [<cite idref="PUB00006537"/>]. It is present in most living organisms, and the cognate structural gene belongs to the so-called minimum gene set [<cite idref="PUB00015591"/>, <cite idref="PUB00015592"/>].</p><p>The domains: MsrA and MsrB, reduce different epimeric forms of methionine sulphoxide. This group represents MsrB, the crystal structure of which has been determined to 1.8A [<cite idref="PUB00014251"/>]. The overall structure shows no resemblance to the structures of MsrA (<db_xref db="INTERPRO" dbkey="IPR002569"/>) from other organisms; though the active sites show approximate mirror symmetry. In each case, conserved amino acid motifs mediate the stereo-specific recognition and reduction of the substrate. Unlike the MsrA domain, the MsrB domain activates the cysteine or selenocysteine nucleophile through a unique Cys-Arg-Asp/Glu catalytic triad. The collapse of the reaction intermediate most likely results in the formation of a sulphenic or selenenic acid moiety. Regeneration of the active site occurs through a series of thiol-disulphide exchange steps involving another active site Cys residue and thioredoxin.</p><p>In a number of pathogenic bacteria, including <taxon tax_id="485">Neisseria gonorrhoeae</taxon>, the MsrA and MsrB domains are fused; the MsrA being N-terminal to MsrB. This arrangement is reversed in <taxon tax_id="160">Treponema pallidum</taxon>. In N. gonorrhoeae and <taxon tax_id="487">Neisseria meningitidis</taxon>, a thioredoxin domain is fused to the N terminus. This may function to reduce the active sites of the downstream MsrA and MsrB domains. </p>