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| | <StructureSection load='4xnv' size='340' side='right'caption='[[4xnv]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='4xnv' size='340' side='right'caption='[[4xnv]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4xnv]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_pasteurianus"_(winogradsky_1895)_lehmann_and_neumann_1907 "bacillus pasteurianus" (winogradsky 1895) lehmann and neumann 1907]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XNV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XNV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4xnv]] is a 1 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=4XNV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XNV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=BUR:1-[2-(2-TERT-BUTYLPHENOXY)PYRIDIN-3-YL]-3-[4-(TRIFLUOROMETHOXY)PHENYL]UREA'>BUR</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xnw|4xnw]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=BUR:1-[2-(2-TERT-BUTYLPHENOXY)PYRIDIN-3-YL]-3-[4-(TRIFLUOROMETHOXY)PHENYL]UREA'>BUR</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">P2RY1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1501 "Bacillus pasteurianus" (Winogradsky 1895) Lehmann and Neumann 1907])</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=4xnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xnv OCA], [https://pdbe.org/4xnv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xnv RCSB], [https://www.ebi.ac.uk/pdbsum/4xnv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xnv ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4xnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xnv OCA], [http://pdbe.org/4xnv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xnv RCSB], [http://www.ebi.ac.uk/pdbsum/4xnv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xnv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == 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> | + | [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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Clostridium pasteurianum]] |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: GPCR, GPCR Network]]
| + | [[Category: Gao Z]] |
| - | [[Category: Gao, Z]] | + | [[Category: Han GW]] |
| - | [[Category: Han, G W]] | + | [[Category: Jacobson K]] |
| - | [[Category: Jacobson, K]] | + | [[Category: Stevens R]] |
| - | [[Category: Stevens, R]] | + | [[Category: Wu B]] |
| - | [[Category: Wu, B]] | + | [[Category: Zhang D]] |
| - | [[Category: Zhang, D]] | + | [[Category: Zhao Q]] |
| - | [[Category: Zhao, Q]] | + | |
| - | [[Category: G protein coupled receptor]]
| + | |
| - | [[Category: Gpcr]]
| + | |
| - | [[Category: Gpcr network]]
| + | |
| - | [[Category: Human p2y1 receptor]]
| + | |
| - | [[Category: Inhibitor complex]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Platelet activation]]
| + | |
| - | [[Category: Psi-biology]]
| + | |
| - | [[Category: Structural genomic]]
| + | |
| - | [[Category: Transport protein-inhibitor complex]]
| + | |
| Structural highlights
4xnv is a 1 chain structure with sequence from Clostridium pasteurianum and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.2Å |
| Ligands: | , , , , , |
| 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.[1] 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.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jin J, Daniel JL, Kunapuli SP. Molecular basis for ADP-induced platelet activation. II. The P2Y1 receptor mediates ADP-induced intracellular calcium mobilization and shape change in platelets. J Biol Chem. 1998 Jan 23;273(4):2030-4. PMID:9442040
- ↑ 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. Two disparate ligand-binding sites in the human P2Y1 receptor. Nature. 2015 Apr 16;520(7547):317-21. doi: 10.1038/nature14287. Epub 2015 Mar 30. PMID:25822790 doi:http://dx.doi.org/10.1038/nature14287
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