Diastereoselective reduction of protein-bound methionine sulfoxide by methionine sulfoxide reductase

Methionine sulfoxide (MetSO) in calmodulin (CaM) was previously shown to be a substrate for bovine liver peptide methionine sulfoxide reductase (pMSR, EC 1.8.4.6), which can partially recover protein structure and function of oxidized CaM in vitro, Here, me report for the first time that pMSR select ively reduces the D-sulfoxide diastereomer of CaM-bound L-MetSO (L-Met-D-SO ), After exhaustive reduction by pMSR, the ratio of L-Met-D-SO to L-Met-D-S O decreased to about 1:25 for hydrogen peroxide-oxidized CaM, and to about 1:10 for free MetSO. The accumulation of MetSO upon oxidative stress and ag ing in vivo may be related to incomplete, diastereoselective, repair by pMS R, (C) 1999 Federation of European Biochemical Societies.