Structure and mechanism of peptide methionine sulfoxide reductase, an "anti-oxidation" enzyme

Peptide methionine sulfoxide reductase (MsrA) reverses oxidative damage to both free methionine and methionine within proteins. As such, it helps prot ect the host organism against stochastic damage that can contribute to cell death. The structure of bovine MsrA has been determined in two different m odifications, both of which provide different insights into the biology of the protein. There are three cysteine residues located in the vicinity of t he active site. Conformational changes in a glycine-rich C-terminal tail ap pear to allow all three thiols to come together and to participate in catal ysis. The structures support a unique, thiol-disulfide exchange mechanism t hat relies upon an essential cysteine as a nucleophile and additional conse rved residues that interact with the oxygen atom of the sulfoxide moiety.