The metabolic enzyme isocitrate dehydrogenase 1 (IDH1) catalyzes the NADP+ -dependent conversion of isocitrate to α-ketoglutarate (αKG). Mutations in IDH1, which primarily affect the R132 residue, can cause a neomorphic reaction where αKG is converted to D-2-hydroxyglutarate (D2HG). The catalytic efficiencies of D2HG production can vary greatly between IDH1 mutants. The arginine to histidine mutation at site 132, R132H, is one of the most common mutations identified in patients with lower grade gliomas and secondary glioblastomas and weakly drives D2HG formation. We have shown previously that smaller residues at residue R132, like R132G, drive more efficient D2HG formation. Here, we propose to study the kinetic features of an arginine to alanine mutation, R132A, an experimental mutation that is yet to be explored. Through steady-state kinetic analysis of the R132A mutation, we can gain a better understanding of what chemical and structural features can facilitate the neomorphic reaction.

Kinetic mechanisms of isocitrate dehydrogenase 1 (IDH1) mutants

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.