Fig. 6: Deuterium uptake by IDH1 WT, R132Q, and R132H in helices bounding the substrate binding pocket.

Deuterium uptake is shown as a gradient from red (high uptake) to blue (low uptake). A Deuterium uptake by IDH1 WT, R132Q, and R132H upon no ligand treatment. These HDX-MS data were overlaid on NADP(H)-only bound forms of WT¹³ in all three cases, as the αKG helix was disordered in the NADP(H)-only bound forms of IDH1 R132Q and R132H³⁰. B Deuterium uptake by WT and R132Q upon treatment with NADP⁺ and ICT, and by IDH1 R132Q and R132H upon treatment with NADPH and αKG. These HDX-MS data were overlaid on WT:NADP(H):ICT:Ca^2+ 13, R132Q:NADP(H):ICT:Ca²⁺ and R132Q:NADP(H):αKG:Ca²⁺, or R132H:NADP(H): αKG:Ca^2+ 14. C Deuterium uptake by IDH1 WT and R132Q upon treatment with NADP⁺, ICT, and Ca²⁺, and by IDH1 R132Q and R132H upon treatment with NADPH, αKG, and Ca²⁺. These HDX-MS data were overlaid on the structures described in (B).