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Vladimir I. Muronetz, Maria V. Medvedeva, Elena V. Schmalhausen
Posttranslational
modifications of the sulfhydryl group of the cysteine residue of
glyceraldehyde-3-phosphate dehydrogenase
Abstract
Abstract. This review considers the main
types of oxidative posttranslational modifications of the glycolytic enzyme
glyceraldehyde-3-phosphate dehydrogenase (GAPDH) targeting the sulfhydryl group
of the catalytic cysteine residue Cys152. The highly reactive sulfhydryl group
of Cys152 in the active centre of GAPDH undergoes oxidation and
S-nitrosylation, leading to enzyme inactivation and destabilization. Upon
reversible oxidation of the sulfhydryl group to form cysteine-sulfenic acid,
the enzyme loses dehydrogenase activity, but gains the ability to catalyze the
acyl-phosphatase reaction. Hydrolysis of the product of the dehydrogenase
reaction, 1,3-diphosphoglycerate, under the action of the oxidized GAPDH leads
to uncoupling of oxidation and phosphorylation at this stage of glycolysis. The
action of nitric oxide results in S-nitrosylation of Cys152 GAPDH and the
subsequent formation of cysteine-sulfenic acid due to hydrolysis of the
S–NO-group. Data are presented on the relationship between S-nitrosylation of
the catalytic Cys152 of GAPDH and its oxidation followed by S-glutathionylation
of the enzyme at Cys152. The role of posttranslational modifications of the
sulfhydryl group of the catalytic cysteine residue in the regulation of enzyme
activity, as well as the mechanisms ensuring the reversibility of such
modifications are discussed.
Key words: glyceraldehyde-3-phosphate
dehydrogenase, reactive oxygen species, sulfhydryl groups, oxidation,
S-nitrosylation, S-glutathionylation
Copyright (C) Chemistry Dept., Moscow State University, 2002
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