Peptide methionine sulfoxide reductase superfamily

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 [10841552]. It is present in most living organisms, and the cognate structural gene belongs to the so-called minimum gene set [8994848, 8816789].

The domains: MsrA and MsrB, reduce different epimeric forms of methionine sulphoxide. This group represent MsrA, the crystal structure of which has been determined in a number of organisms. In Mycobacterium tuberculosis, the MsrA structure has been determined to 1.5 A¿ resolution [12837786]. In contrast to the three catalytic cysteine residues found in previously characterised MsrA structures, M. tuberculosis MsrA represents a class containing only two functional cysteine residues. The overall structure shows no resemblance to the structures of MsrB 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.

In a number of pathogenic bacteria including Neisseria gonorrhoeae, the MsrA and MsrB domains are fused; the MsrA being N-terminal to MsrB. This arrangement is reversed in Treponema pallidum. In N. gonorrhoeae and Neisseria meningitidis a thioredoxin domain is fused to the N-terminus. This may function to reduce the active sites of the downstream MsrA and MsrB domains.