4XNV
The human P2Y1 receptor in complex with BPTU
Summary for 4XNV
| Entry DOI | 10.2210/pdb4xnv/pdb |
| Related | 4XNW |
| Descriptor | P2Y purinoceptor 1, Rubredoxin, P2Y purinoceptor 1, 1-[2-(2-tert-butylphenoxy)pyridin-3-yl]-3-[4-(trifluoromethoxy)phenyl]urea, CHOLESTEROL, ... (8 entities in total) |
| Functional Keywords | human p2y1 receptor, g protein coupled receptor, platelet activation, membrane protein, inhibitor complex, transport protein-inhibitor complex, psi-biology, structural genomics, gpcr network, gpcr, transport protein/inhibitor |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 52916.56 |
| Authors | Zhang, D.,Gao, Z.,Jacobson, K.,Han, G.W.,Stevens, R.,Zhao, Q.,Wu, B.,GPCR Network (GPCR) (deposition date: 2015-01-16, release date: 2015-04-01, Last modification date: 2024-10-30) |
| Primary citation | Zhang, D.,Gao, Z.G.,Zhang, K.,Kiselev, E.,Crane, S.,Wang, J.,Paoletta, S.,Yi, C.,Ma, L.,Zhang, W.,Han, G.W.,Liu, H.,Cherezov, V.,Katritch, V.,Jiang, H.,Stevens, R.C.,Jacobson, K.A.,Zhao, Q.,Wu, B. Two disparate ligand-binding sites in the human P2Y1 receptor Nature, 520:317-321, 2015 Cited by PubMed Abstract: 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 Å resolution, and with a non-nucleotide antagonist BPTU at 2.2 Å 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. PubMed: 25822790DOI: 10.1038/nature14287 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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