Molecular basis for the function of the αβ heterodimer of human NAD-dependent isocitrate dehydrogenase.

ABSTRACT: Mammalian mitochondrial NAD-dependent isocitrate dehydrogenase (NAD-IDH) catalyzes the decarboxylation of isocitrate into α-ketoglutarate in the tricarboxylic acid cycle. It exists as the α₂βγ heterotetramer composed of the αβ and αγ heterodimers. Different from the αγ heterodimer that can be allosterically activated by CIT and ADP, the αβ heterodimer cannot be allosterically regulated by the activators; however, the molecular mechanism is unclear. We report here the crystal structures of the αβ heterodimer of human NAD-IDH with the α subunit in apo form and in Ca²⁺-bound, NAD-bound, and NADH-bound forms. Structural analyses and comparisons reveal that the αβ heterodimer has a similar yet more compact overall structure compared with the αγ heterodimer and contains a p

SUBMITTER: Sun P 

PROVIDER: S-EPMC6827300 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature