Molecular mechanism of the allosteric regulation of the αγ heterodimer of human NAD-dependent isocitrate dehydrogenase.

ABSTRACT: Human NAD-dependent isocitrate dehydrogenase catalyzes the decarboxylation of isocitrate (ICT) into α-ketoglutarate in the Krebs cycle. It exists as the α₂βγ heterotetramer composed of the αβ and αγ heterodimers. Previously, we have demonstrated biochemically that the α₂βγ heterotetramer and αγ heterodimer can be allosterically activated by citrate (CIT) and ADP. In this work, we report the crystal structures of the αγ heterodimer with the γ subunit bound without or with different activators. Structural analyses show that CIT, ADP and Mg²⁺ bind adjacent to each other at the allosteric site. The CIT binding induces conformational changes at the allosteric site, which are transmitted to the active site through the heterodimer interface, leading to stabilizati

SUBMITTER: Ma T 

PROVIDER: S-EPMC5241874 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature