Molecular Recognition of Agonists and Antagonists by the Nucleotide-Activated G Protein-Coupled P2Y2 Receptor
作者： Muhammad Rafehi , Alexander Neumann , Younis Baqi , Enas M. Malik , Michael Wiese
DOI: 10.1021/ACS.JMEDCHEM.7B00854
关键词: Purinergic P2Y Receptor Agonists 、 G protein 、 Biochemistry 、 Receptor 、 Chemistry 、 Purinergic P2Y Receptor Antagonists 、 Docking (molecular) 、 Virtual screening 、 Agonist 、 Homology modeling 、 Molecular medicine 、 Drug discovery
摘要: A homology model of the nucleotide-activated P2Y2R was created based on X-ray structures P2Y1 receptor. Docking studies were performed, and receptor mutants to probe identified binding interactions. Mutation residues predicted interact with ribose (Arg110) phosphates nucleotide agonists (Arg265, Arg292) or that contribute indirectly (Tyr288) abolished activity. The Y114F, R194A, F261A mutations led inactivity diadenosine tetraphosphate a reduced response UTP. Significant reduction in agonist potency observed for all other (Phe111, His184, Ser193, Phe261, Tyr268, Tyr269) be involved recognition. An ionic lock between Asp185 Arg292 is probably activation interacts phosphate groups. antagonist AR-C118925 anthraquinones likely bind orthosteric site. updated models will useful virtual screening drug design.
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