Fig. 1. Dimerisation of IDH1.
Two wild-type IDH1 monomers form a catalytic homodimer, which transforms isocitrate into α-KG. In IDH1-mutated cells, a catalytic heterodimer is formed with one wild-type monomer and one monomer carrying the R132H mutant. The heterodimer exhibits neomorphic activity, which consumes α-KG for D-2-HG synthesis. Biochemical studies indicate that a homodimer formed by two IDH1 mutant monomer is not catalytically active. Molecular modelling is based on the published crystal structures 1T09,6 3MAS and 3MAP.111