4xnv
From Proteopedia
(Difference between revisions)
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/P2RY1_HUMAN 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.<ref>PMID:9442040</ref> | [[http://www.uniprot.org/uniprot/P2RY1_HUMAN 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.<ref>PMID:9442040</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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. | ||
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| + | 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<ref>PMID:25822790</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 06:51, 22 April 2015
The human P2Y1 receptor in complex with BPTU
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