Studies on the regulatory mechanism of isocitrate dehydrogenase 2 using acetylation mimics.

ABSTRACT: Mitochondrial isocitrate dehydrogenase 2 (IDH2) converts NADP⁺ to NADPH and promotes regeneration of reduced glutathione (GSH) by supplying NADPH to glutathione reductase or thioredoxin reductase. We have previously shown that under calorie restriction, mitochondrial deacetylase Sirt3 deacetylates and activates IDH2, thereby regulating the mitochondrial glutathione antioxidant defense system in mice. To investigate the regulatory mechanism of mIDH2 (mouse mitochondrial IDH2), we used lysine-to-glutamine (KQ) mutants to mimic acetylated lysines and screened 15 KQ mutants. Among these mutants, the activities of the K256Q and K413Q proteins were less than 50% of the wild-type value. We then solved the crystal structures of the wild-type mIDH2 and the K256Q mutant proteins, revealin

SUBMITTER: Xu Y 

PROVIDER: S-EPMC5575304 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature