Figure 2.

Structural modeling of IDH1 mutations identified in tumors. A, the structure of WT IDH1 complexed with ICT, NADP⁺, and Ca²⁺ (PDB 1T0L (33)) and B, R132H IDH1 complexed with αKG, NADP⁺, and Ca²⁺ (PDB 4KZO (27)) were used to model additional mutations. In both panels, WT IDH1 is shown in green, A134D in cyan, H133Q in black, R100Q in dark blue, R132H in orange, R132C in yellow, and R132G in gray. Substrates and residues that are mutated are highlighted in stick format, as well as catalytic residue Tyr-139. Ca²⁺ is shown as a sphere. Ligand restraint generation and optimization of provided cif files were generated using eLBOW in the Phenix software suite (35), and mutations were made using Coot (54). Geometry Minimization (Phenix software suite) (35) was used to regularize geometries of the models, with 500 iterations and 5 macro cycles.