Structural analysis of oncogenic mutation of isocitrate dehydrogenase 1.

摘要: Arginine to histidine mutation at position 132 (R132H) in isocitrate dehydrogenase 1 (IDH1) led reduced affinity of the respective enzymes for and increased α-ketoglutarate (AKG) NADPH. This phenomenon retarded oxidative decarboxylation AKG conferred a novel enzymatic activity that facilitated reduction D-2-hydroxyglutarate (D-2HG). The loss utilization gain 2HG production from IDH1 R132H had been taken up as fundamental problem solve this, structural biology approaches were adopted. Interaction analysis was carried out investigate substrate binding environment. altered behaviour mutant native interaction explored by performing long-term molecular dynamics simulations (∼300 ns). study reports comprehensive atomic gain-of-function enzyme which turn provides direction towards new therapeutics.