View source for 4xnw


==The human P2Y1 receptor in complex with MRS2500==
<StructureSection load='4xnw' size='340' side='right'caption='[[4xnw]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4xnw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_pasteurianum Clostridium pasteurianum] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XNW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XNW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2ID:[(1R,2S,4S,5S)-4-[2-IODO-6-(METHYLAMINO)-9H-PURIN-9-YL]-2-(PHOSPHONOOXY)BICYCLO[3.1.0]HEX-1-YL]METHYL+DIHYDROGEN+PHOSPHATE'>2ID</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4xnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xnw OCA], [https://pdbe.org/4xnw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xnw RCSB], [https://www.ebi.ac.uk/pdbsum/4xnw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xnw ProSAT]</span></td></tr>
</table>
== Function ==
[https://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> [https://www.uniprot.org/uniprot/RUBR_CLOPA RUBR_CLOPA] Rubredoxin is a small nonheme, iron protein lacking acid-labile sulfide. Its single Fe, chelated to 4 Cys, functions as an electron acceptor and may also stabilize the conformation of the molecule.
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== 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<ref>PMID:25822790</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4xnw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Clostridium pasteurianum]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gao Z]]
[[Category: Han GW]]
[[Category: Jacobson K]]
[[Category: Stevens R]]
[[Category: Wu B]]
[[Category: Zhang D]]
[[Category: Zhao Q]]