Structure and allosteric regulation of human NAD-dependent isocitrate dehydrogenase.

ABSTRACT: Human NAD-dependent isocitrate dehydrogenase or HsIDH3 catalyzes the decarboxylation of isocitrate into α-ketoglutarate in the TCA cycle. HsIDH3 exists and functions as a heterooctamer composed of the αβ and αγ heterodimers, and is regulated allosterically and/or competitively by numerous metabolites including CIT, ADP, ATP, and NADH. In this work, we report the crystal structure of HsIDH3 containing a β mutant in apo form. In the HsIDH3 structure, the αβ and αγ heterodimers form the α₂βγ heterotetramer via their clasp domains, and two α₂βγ heterotetramers form the (α₂βγ)₂ heterooctamer through insertion of the N-terminus of the γ subunit of one heterotetramer into the back cleft of the β subunit of the other heterotetramer. The functional roles

SUBMITTER: Sun P 

PROVIDER: S-EPMC7752914 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature