4xnv

The human P2Y1 receptor in complex with BPTU

spinqualitylabelsall models 4xnv, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4xnv is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 1PE, BUR, CLR, OLC, Y01, ZN Related: 4xnw Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [P2RY1_HUMAN] Receptor for extracellular adenine nucleotides such as ATP and ADP. In platelets binding to ADP leads to mobilization of intracellular calcium ions via activation of phospholipase C, a change in platelet shape, and probably to platelet aggregation. Publication Abstract from PubMed In response to adenosine 5'-diphosphate, the P2Y1 receptor (P2Y1R) facilitates platelet aggregation, and thus serves as an important antithrombotic drug target. Here we report the crystal structures of the human P2Y1R in complex with a nucleotide antagonist MRS2500 at 2.7 A resolution, and with a non-nucleotide antagonist BPTU at 2.2 A resolution. The structures reveal two distinct ligand-binding sites, providing atomic details of P2Y1R's unique ligand-binding modes. MRS2500 recognizes a binding site within the seven transmembrane bundle of P2Y1R, which is different in shape and location from the nucleotide binding site in the previously determined structure of P2Y12R, representative of another P2YR subfamily. BPTU binds to an allosteric pocket on the external receptor interface with the lipid bilayer, making it the first structurally characterized selective G-protein-coupled receptor (GPCR) ligand located entirely outside of the helical bundle. These high-resolution insights into P2Y1R should enable discovery of new orthosteric and allosteric antithrombotic drugs with reduced adverse effects. Two disparate ligand-binding sites in the human P2Y1 receptor.,Zhang D, Gao ZG, Zhang K, Kiselev E, Crane S, Wang J, Paoletta S, Yi C, Ma L, Zhang W, Han GW, Liu H, Cherezov V, Katritch V, Jiang H, Stevens RC, Jacobson KA, Zhao Q, Wu B Nature. 2015 Apr 16;520(7547):317-21. doi: 10.1038/nature14287. Epub 2015 Mar 30. PMID:25822790 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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