ROLE OF METHIONINE RESIDUES IN ENZYME REGULATION

Heart, Lung, And Blood Institute

Investigators

Abstract

Earlier studies in this laboratory established that the cyclic oxidation-reduction of methionine residues of proteins can serve an antioxidant function to protect cells from damage by reactive oxygen species (R0S). The possibility that cyclic oxidation-reduction of methionine residues of proteins may also play an important role in the regulation of some enzyme activities is suggested by the observations: (a) The ROS-dependent oxidation of methionine residues of some enzymes to methionine sulfoxide [Met(0)] leads to loss of activity and (b) activity of such oxidized enzymes can be restored by the thioredoxin-dependent reduction of the Met(0) back to methionine by the action of peptide methionine sulfoxide reductase (MSR). If the cyclic oxidation-reduction of methionine residues is a means of cellular regulation, cells should contain specific oxidases that can selectively oxidize methionine residues of the regulatory enzymes. We have initiated a study to search for such enzymes using phosphofructokinase and calmodulin as potential targets, since the activities of these proteins are severely altered by oxidation or substitutions of unique methionine residues.