Evaluation of a previous model for ADPR binding to the NUDT9-H domain. (A) The previously proposed orientation of ADPR shown in the NUDT9-H domain using our present model. In this orientation, ADPR is in close proximity to several residues for which mutations did not affect binding. Current traces of WT TRPM2 (B) and mutants at three positions (C–E) predicted to interact with ADPR in the orientation shown in A. (F) Summary of the currents from the mutants at the three positions when activated by ADPR 100 µM. Data are expressed as mean ± SEM from at least five independent repetitions.