InterPro domain: IPR036509

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 [ 1 ]. It is present in most living organisms, and the cognate structural gene belongs to the so-called minimum gene set [ 2 , 3 ].

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 Angstrom resolution [ 4 ]. 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 ( IPR002579 ) 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.

1. Thiol-disulfide exchange is involved in the catalytic mechanism of peptide methionine sulfoxide reductase. Proc. Natl. Acad. Sci. U.S.A. 97, 6463-8
2. Complete genome sequences of cellular life forms: glimpses of theoretical evolutionary genomics. Curr. Opin. Genet. Dev. 6, 757-62
3. A minimal gene set for cellular life derived by comparison of complete bacterial genomes. Proc. Natl. Acad. Sci. U.S.A. 93, 10268-73
4. Structure of Mycobacterium tuberculosis methionine sulfoxide reductase A in complex with protein-bound methionine. J. Bacteriol. 185, 4119-26