X-ray structures of endothelin ETB receptor bound to clinical antagonist bosentan and its analog

Nature Structural and Molecular Biology

Volumn 24, Issue 9, 2017, Pages 758-764

  Shihoya, Wataru ^a,b   Nishizawa, Tomohiro ^b,c   Yamashita, Keitaro ^d   Inoue, Asuka ^c,e   Hirata, Kunio ^c,d   Kadji, Francois Marie Ngako ^e   Okuta, Akiko ^a   Tani, Kazutoshi ^a   Aoki, Junken ^e,f   Fujiyoshi, Yoshinori ^a   Doi, Tomoko ^g   Nureki, Osamu ^b  

^a NAGOYA UNIVERSITY   (Japan)

^b UNIVERSITY OF TOKYO   (Japan)

^c JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

^d RIKEN SPring 8 Center ^*  (Japan)

^e TOHOKU UNIVERSITY   (Japan)

^f JAPAN AGENCY FOR MEDICAL RESEARCH AND DEVELOPMENT   (Japan)

^g KYOTO UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

BOSENTAN; ENDOTHELIN B RECEPTOR; ENDOTHELIN DERIVATIVE; OPIATE RECEPTOR; OREXIN 2 RECEPTOR; EDNRB PROTEIN, HUMAN; ENDOTHELIN RECEPTOR ANTAGONIST; PROTEIN BINDING; SULFONAMIDE;

ALLOSTERISM; ARTICLE; BINDING SITE; COMPARATIVE STUDY; CONTROLLED STUDY; DRUG BINDING SITE; HUMAN; HYDROGEN BOND; IC50; LIGAND BINDING; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN STRUCTURE; CHEMISTRY; METABOLISM; MOLECULAR MODEL; X RAY CRYSTALLOGRAPHY;

CRYSTALLOGRAPHY, X-RAY; ENDOTHELIN RECEPTOR ANTAGONISTS; HUMANS; MODELS, MOLECULAR; PROTEIN BINDING; PROTEIN CONFORMATION; RECEPTOR, ENDOTHELIN B; SULFONAMIDES;

EID: 85029088435     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.3450     Document Type: Article

References (64)

1. Yanagisawa, M. et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332, 411-415 (1988).
2. Arai, H., Hori, S., Aramori, I., Ohkubo, H. & Nakanishi, S. Cloning and expression of a cDNA encoding an endothelin receptor. Nature 348, 730-732 (1990).
3. Sakurai, T. et al. Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor. Nature 348, 732-735 (1990).
4. Kedzierski, R. M. & Yanagisawa, M. Endothelin system: the double-edged sword in health and disease. Annu. Rev. Pharmacol. Toxicol. 41, 851-876 (2001).
5. Kohan, D. E., Rossi, N. F., Inscho, E. W. & Pollock, D. M. Regulation of blood pressure and salt homeostasis by endothelin. Physiol. Rev. 91, 1-77 (2011).
6. Rubanyi, G. M. & Polokoff, M. A. Endothelins: molecular biology, biochemistry, pharmacology, physiology, and pathophysiology. Pharmacol. Rev. 46, 325-415 (1994).
7. Shin, M. K., Levorse, J. M., Ingram, R. S. & Tilghman, S. M. The temporal requirement for endothelin receptor-B signalling during neural crest development. Nature 402, 496-501 (1999).
8. Remuzzi, G., Perico, N. & Benigni, A. New therapeutics that antagonize endothelin: promises and frustrations. Nat. Rev. Drug Discov. 1, 986-1001 (2002).
9. Channick, R. N. et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 358, 1119-1123 (2001).
10. Rubin, L. J. et al. Bosentan therapy for pulmonary arterial hypertension. N. Engl. J. Med. 346, 896-903 (2002).
11. Dhaun, N., Goddard, J. & Webb, D. J. The endothelin system and its antagonism in chronic kidney disease. J. Am. Soc. Nephrol. 17, 943-955 (2006).
12. Rosanò, L., Spinella, F. & Bagnato, A. Endothelin 1 in cancer: biological implications and therapeutic opportunities. Nat. Rev. Cancer 13, 637-651 (2013).
13. Clozel, M. et al. Pharmacological characterization of bosentan, a new potent orally active nonpeptide endothelin receptor antagonist. J. Pharmacol. Exp. Ther. 270, 228-235 (1994).
14. Clozel, M. et al. Pathophysiological role of endothelin revealed by the first orally active endothelin receptor antagonist. Nature 365, 759-761 (1993).
15. Neidhart, W. et al. The discovery of nonpeptide endothelin receptor antagonists. Progression towards bosentan. Chimia 50, 519-524 (1996).
16. Mucke, H. A. Pulmonary arterial hypertension: on the way to a manageable disease. Curr. Opin. Investig. Drugs 9, 957-962 (2008).
17. Norman, P. Pulmonary arterial hypertension: a rare disease that encourages the development of multiple treatments. Expert Opin. Orphan Drugs 2, 1137-1145 (2014).
18. Korn, J. H. et al. Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist. Arthritis Rheum. 50, 3985-3993 (2004).
19. Gatfield, J., Mueller Grandjean, C., Bur, D., Bolli, M. H. & Nayler, O. Distinct ETA receptor binding mode of macitentan as determined by site directed mutagenesis. PLoS One 9, e107809 (2014).
20. Gatfield, J., Mueller Grandjean, C., Sasse, T., Clozel, M. & Nayler, O. Slow receptor dissociation kinetics differentiate macitentan from other endothelin receptor antagonists in pulmonary arterial smooth muscle cells. PLoS One 7, e47662 (2012).
21. Krum, H., Viskoper, R. J., Lacourciere, Y., Budde, M. & Charlon, V. The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. N. Engl. J. Med. 338, 784-790 (1998).
22. Bolli, M. H. et al. The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N?-propylsulfamide (macitentan), an orally active, potent dual endothelin receptor antagonist. J. Med. Chem. 55, 7849-7861 (2012).
23. Vatter, H. & Seifert, V. Ambrisentan, a non-peptide endothelin receptor antagonist. Cardiovasc. Drug Rev. 24, 63-76 (2006).
24. Barst, R. J. et al. Sitaxsentan therapy for pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 169, 441-447 (2004).
25. Boss, C., Bolli, M. H. & Gatfield, J. From bosentan (Tracleer®) to macitentan (Opsumit®): the medicinal chemistry perspective. Bioorg. Med. Chem. Lett. 26, 3381-3394 (2016).
26. Kholdani, C. A., Fares, W. H. & Trow, T. K. Macitentan for the treatment of pulmonary arterial hypertension. Vasc. Health Risk Manag. 10, 665-673 (2014).
27. Shihoya, W. et al. Activation mechanism of endothelin ETB receptor by endothelin-1 Nature 537, 363-368 (2016).
28. Sawaki, M. et al. Chronic effects of an orally active selective endothelin-B-receptor antagonist in experimental congestive heart failure. J. Cardiovasc. Pharmacol. 36, S323-S326 (2000).
29. Okuta, A., Tani, K., Nishimura, S., Fujiyoshi, Y. & Doi, T. Thermostabilization of the human endothelin type B receptor. J. Mol. Biol. 428, 2265-2274 (2016).
30. Hattori, M., Hibbs, R. E. & Gouaux, E. A fluorescence-detection size-exclusion chromatography-based thermostability assay for membrane protein precrystallization screening. Structure 20, 1293-1299 (2012).
31. Parker, M. S., Wong, Y. Y. & Parker, S. L. An ion-responsive motif in the second transmembrane segment of rhodopsin-like receptors. Amino Acids 35, 1-15 (2008).
32. Katritch, V. et al. Allosteric sodium in class A GPCR signaling. Trends Biochem. Sci. 39, 233-244 (2014).
33. Liu, W. et al. Structural basis for allosteric regulation of GPCRs by sodium ions. Science 337, 232-236 (2012).
34. Miller-Gallacher, J. L. et al. The 2. 1 Å resolution structure of cyanopindolol-bound ?1-adrenoceptor identifies an intramembrane Na+ ion that stabilises the ligand-free receptor. PLoS One 9, e92727 (2014).
35. Fenalti, G. et al. Molecular control of ?-opioid receptor signalling. Nature 506, 191-196 (2014).
36. Zhang, C. et al. High-resolution crystal structure of human protease-activated receptor 1. Nature 492, 387-392 (2012).
37. Harding, M. M. Metal-ligand geometry relevant to proteins and in proteins: sodium and potassium. Acta Crystallogr. D Biol. Crystallogr. 58, 872-874 (2002).
38. White, J. F. et al. Structure of the agonist-bound neurotensin receptor. Nature 490, 508-513 (2012).
39. Yin, J., Mobarec, J. C., Kolb, P. & Rosenbaum, D. M. Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant. Nature 519, 247-250 (2015).
40. Thompson, A. A. et al. Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic. Nature 485, 395-399 (2012).
41. Takasuka, T., Sakurai, T., Goto, K., Furuichi, Y. & Watanabe, T. Human endothelin receptor ETB. Amino acid sequence requirements for super stable complex formation with its ligand. J. Biol. Chem. 269, 7509-7513 (1994).
42. Rose, P. M. et al. Aspartate mutation distinguishes ETA but not ETB receptor subtypeselective ligand binding while abolishing phospholipase C activation in both receptors. FEBS Lett. 361, 243-249 (1995).
43. Opgenorth, T. J. et al. Pharmacological characterization of A-127722: an orally active and highly potent ETA-selective receptor antagonist. J. Pharmacol. Exp. Ther. 276, 473-481 (1996).
44. Winn, M. et al. 2, 4-Diarylpyrrolidine-3-carboxylic acids-potent ETA selective endothelin receptor antagonists. 1. Discovery of A-127722. J. Med. Chem. 39, 1039-1048 (1996).
45. Kikuchi, T. et al. Endothelin-1 analogues substituted at both position 18 and 19: highly potent endothelin antagonists with no selectivity for either receptor subtype ETA or ETB. J. Med. Chem. 36, 4087-4093 (1993).
46. Tam, J. P. et al. Alanine scan of endothelin: importance of aromatic residues. Peptides 15, 703-708 (1994).
47. Rovero, P., Patacchini, R. & Maggi, C. A. Structure-activity studies on endothelin (16-21), the C-terminal hexapeptide of the endothelins, in the guinea-pig bronchus. Br. J. Pharmacol. 101, 232-234 (1990).
48. Henry, J. A., Horwell, D. C., Meecham, K. G. & Rees, D. C. A structure-affinity study of the amino-acid side-chains in neurotensin-N and C-terminal deletions and Ala-scan. Bioorg. Med. Chem. Lett. 3, 949-952 (1993).
49. Guerrini, R. et al. Address and message sequences for the nociceptin receptor: a structure-activity study of nociceptin-(1-13)-peptide amide. J. Med. Chem. 40, 1789-1793 (1997).
50. Nakajima, K. et al. Structure-activity relationship of endothelin: importance of charged groups. Biochem. Biophys. Res. Commun. 163, 424-429 (1989).
51. Vagner, J., Qu, H. & Hruby, V. J. Peptidomimetics, a synthetic tool of drug discovery. Curr. Opin. Chem. Biol. 12, 292-296 (2008).
52. Hruby, V. J. Designing peptide receptor agonists and antagonists. Nat. Rev. Drug Discov. 1, 847-858 (2002).
53. Caffrey, M. & Cherezov, V. Crystallizing membrane proteins using lipidic mesophases. Nat. Protoc. 4, 706-731 (2009).
54. Kabsch, W. Xds. Acta Crystallogr. D Biol. Crystallogr. 66, 125-132 (2010).
55. Ueno, G. et al. Remote access and automation of SPring-8 MX beamlines. AIP Conf. Proc. 1741, 050021 (2016).
56. Kabsch, W. Processing of X-ray snapshots from crystals in random orientations. Acta Crystallogr. D Biol. Crystallogr. 70, 2204-2216 (2014).
57. McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658-674 (2007).
58. Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486-501 (2010).
59. Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213-221 (2010).
60. Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr. 66, 12-21 (2010).
61. Inoue, A. et al. TGF? shedding assay: an accurate and versatile method for detecting GPCR activation. Nat. Methods 9, 1021-1029 (2012).
62. Doi, T., Sugimoto, H., Arimoto, I., Hiroaki, Y. & Fujiyoshi, Y. Interactions of endothelin receptor subtypes A and B with Gi, Go, and Gq in reconstituted phospholipid vesicles. Biochemistry 38, 3090-3099 (1999).
63. Wada, K. et al. Purification of an endothelin receptor from human placenta. Biochem. Biophys. Res. Commun. 167, 251-257 (1990).
64. Elshourbagy, N. A. et al. Molecular cloning and characterization of the major endothelin receptor subtype in porcine cerebellum. Mol. Pharmacol. 41, 465-473 (1992).