Physical Sciences and Mathematics Commons^™

Crucial Positively Charged Residues For Ligand Activation Of The Gpr35 Receptor, Pingwei Zhao, Tom R. Lane, Helen G.L. Gao, Dow P. Hurst, Evangelia Kotsikorou, Long Le, Eugen Brailoiu, Patricia H. Reggio, Mary E. Abood

Chemistry Faculty Publications and Presentations

GPR35 is a G protein-coupled receptor expressed in the immune, gastrointestinal, and nervous systems in gastric carcinomas and is implicated in heart failure and pain perception. We investigated residues in GPR35 responsible for ligand activation and the receptor structure in the active state. GPR35 contains numerous positively charged amino acids that face into the binding pocket that cluster in two distinct receptor regions, TMH3-4-5-6 and TMH1-2-7. Computer modeling implicated TMH3-4-5-6 for activation by the GPR35 agonists zaprinast and pamoic acid. Mutation results for the TMH1-2-7 region of GPR35 showed no change in ligand efficacies at the K1.32A, R2.65A, R7.33A, and …