Identification of the ADPR binding pocket in the NUDT9 homology domain of TRPM2.

ABSTRACT: Activation of the transient receptor potential melastatin 2 (TRPM2) channel occurs during the response to oxidative stress under physiological conditions as well as in pathological processes such as ischemia and diabetes. Accumulating evidence indicates that adenosine diphosphate ribose (ADPR) is the most important endogenous ligand of TRPM2. However, although it is known that ADPR binds to the NUDT9 homology (NUDT9-H) domain in the intracellular C-terminal region, the molecular mechanism underlying ADPR binding and activation of TRPM2 remains unknown. In this study, we generate a structural model of the NUDT9-H domain and identify the binding pocket for ADPR using induced docking and molecular dynamics simulation. We find a subset of 11 residues-H1346, T1347, T1349, L1379, G1389, S1391, E

SUBMITTER: Yu P 

PROVIDER: S-EPMC5299621 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature