Structure of the human P2Y12 receptor in complex with an antithrombotic drug

Nature

Volumn 508, Issue 7498, 2014, Pages 115-118

  Zhang, Kaihua ^a   Zhang, Jin ^a   Gao, Zhan Guo ^b   Zhang, Dandan ^a   Zhu, Lan ^a   Han, Gye Won ^c   Moss, Steven M ^b   Paoletta, Silvia ^b   Kiselev, Evgeny ^b   Lu, Weizhen ^a   Fenalti, Gustavo ^c   Zhang, Wenru ^a   Müller, Christa E ^d   Yang, Huaiyu ^a   Jiang, Hualiang ^a   Cherezov, Vadim ^c   Katritch, Vsevolod ^c   Jacobson, Kenneth A ^b   Stevens, Raymond C ^c,e   Wu, Beili ^a   Zhao, Qiang ^a   more..

^a SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

^b NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^c SCRIPPS RESEARCH INSTITUTE   (United States)

^d UNIVERSITY OF BONN   (Germany)

^e SHANGHAITECH UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ANTICOAGULANT AGENT; CLOPIDOGREL; PRASUGREL; PURINERGIC P2Y12 RECEPTOR; TICAGRELOR; DISULFIDE; DRUG DERIVATIVE; ETHYL 6 (4 ((BENZYLSULFONYL)CARBAMOYL)PIPERIDIN 1 YL) 5 CYANO 2 ISOPROPYLNICOTINATE; ETHYL 6-(4-((BENZYLSULFONYL)CARBAMOYL)PIPERIDIN-1-YL)-5-CYANO-2-ISOPROPYLNICOTINATE; FIBRINOLYTIC AGENT; LIGAND; NICOTINIC ACID; P2RY12 PROTEIN, HUMAN; PURINERGIC P2Y RECEPTOR ANTAGONIST; SULFONAMIDE;

ARTICLE; BIOAVAILABILITY; BLOOD CLOTTING; CRYSTAL STRUCTURE; DISULFIDE BOND; DRUG CONFORMATION; DRUG HALF LIFE; GEL PERMEATION CHROMATOGRAPHY; HEART INFARCTION; HUMAN; HYDROGEN BOND; LIGAND BINDING; POINT MUTATION; PRIORITY JOURNAL; THROMBOCYTE ACTIVATION; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; METABOLISM; MOLECULAR DOCKING; PROTEIN CONFORMATION; X RAY CRYSTALLOGRAPHY;

BINDING SITES; CRYSTALLOGRAPHY, X-RAY; DISULFIDES; FIBRINOLYTIC AGENTS; HUMANS; LIGANDS; MODELS, MOLECULAR; MOLECULAR DOCKING SIMULATION; NIACIN; PROTEIN CONFORMATION; PURINERGIC P2Y RECEPTOR ANTAGONISTS; RECEPTORS, PURINERGIC P2Y12; SULFONAMIDES;

EID: 84899755031     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature13083     Document Type: Article

References (36)

1. Abbracchio, M. P. et al. International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol. Rev. 58, 281-341 (2006).
2. Jacobson, K. A. & Boeynaems, J. M. P2Y nucleotide receptors: promise of therapeutic applications. Drug Discov. Today 15, 570-578 (2010).
3. 12 receptor. Eur. J. Med. Chem. 65, 360-375 (2013).
4. 12, play a role in controlling shape change in human platelets. Platelets 14, 15-20 (2003).
5. Wallentin, L. et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N. Engl. J. Med. 361, 1045-1057 (2009).
6. 12 receptor antagonist. Cardiovasc. Ther. 27, 259-274 (2009).
7. 12 receptor oligomers and partitions them out of lipid rafts. Proc. Natl Acad. Sci. USA 103, 11069-11074 (2006).
8. 12 receptor. J. Thromb. Haemost. 6, 1908-1914 (2008).
9. 12/thrombin in ADP- and thrombin-induced human platelet activation. Br. J. Pharmacol. 142, 1325-1331 (2004).
10. 12 receptor. Separation of the antithrombotic effect and bleeding for candidate drug AZD1283. J. Med. Chem. 56, 7015-7024 (2013).
11. Chun, E. et al. Fusion partner toolchest for the stabilization and crystallization of G protein-coupled receptors. Structure 20, 967-976 (2012).
12. Ballesteros, J. & Weinstein, H. Integrated methods for the construction of threedimensional models and computational probing of structure-function relations in G protein-coupled receptors. Methods Neurosci. 25, 366-428 (1995).
13. Fredriksson, R., Lagerstrom, M. C., Lundin, L. G. & Schioth, H. B. The G-proteincoupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol. Pharmacol. 63, 1256-1272 (2003).
14. Hanson, M. A. et al. Crystal structure of a lipid G protein-coupled receptor. Science 335, 851-855 (2012).
15. Zhang, C. et al. High-resolution crystal structure of human protease-activated receptor 1. Nature 492, 387-392 (2012).
16. Chee, M. J. et al. The third intracellular loop stabilizes the inactive state of the neuropeptide Y1 receptor. J. Biol. Chem. 283, 33337-33346 (2008).
17. Schulz, A. & Schöneberg, T. The structural evolution of a P2Y-like G-proteincoupled receptor. J. Biol. Chem. 278, 35531-35541 (2003).
18. Audet, M. & Bouvier, M. Restructuring G-protein-coupled receptor activation. Cell 151, 14-23 (2012).
19. Rader, A. J. et al. Identification of core amino acids stabilizing rhodopsin. Proc. Natl Acad. Sci. USA 101, 7246-7251 (2004).
20. Tan, Q. et al. Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex. Science 341, 1387-1390 (2013).
21. Katritch, V., Cherezov, V. & Stevens, R. C. Structure-function of the G proteincoupled receptor superfamily. Annu. Rev. Pharmacol. Toxicol. 53, 531-556 (2013).
22. 12 receptor when interacting with antagonists. J. Thromb. Haemost. 7, 232-234 (2009).
23. 3H]PSB-0413. Purinergic Signal. 9, 59-66 (2013).
24. Cattaneo, M. The P2 receptors and congenital platelet function defects. Semin. Thromb. Hemost. 31, 168-173 (2005).
25. Ignatovica, V., Megnis, K., Lapins, M., Schiöth, H. B. & Klovins, J. Identification and analysis of functionally important amino acids in human purinergic 12 receptor using a Saccharomyces cerevisiae expression system. FEBS J. 279, 180-191 (2012).
26. 12 receptor for adenosine diphosphate: congenital and drug-induced defects. Blood 117, 2102-2112 (2011).
27. 12 receptor of a patient with congenital bleeding. Proc. Natl Acad. Sci. USA 100, 1978-1983 (2003).
28. 12 receptor. Eur. J. Pharmacol. 644, 10-16 (2010).
29. 12 receptor inhibitor. Thromb. Haemost. 94, 593-598 (2005).
30. Caffrey, M. & Cherezov, V. Crystallizing membrane proteins using lipidic mesophases. Nature Protocols 4, 706-731 (2009).
31. Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307-326 (1997).
32. McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658-674 (2007).
33. Vagin, A. A. et al. REFMAC5 dictionary: organization of prior chemical knowledge and guidelines for its use. Acta Crystallogr. D 60, 2184-2195 (2004).
34. Smart, O. S. et al. Exploiting structure similarity in refinement: automated NCS and target-structure restraints in BUSTER. Acta Crystallogr. D 68, 368-380 (2012).
35. Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486-501 (2010).
36. Madhavi Sastry, G., Adzhigirey, M., Day, T., Annabhimoju, R. & Sherman, W. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J. Comput. Aided Mol. Des. 27, 221-234 (2013).