Biased Agonist TRV027 Determinants in AT1R by Molecular Dynamics Simulations

Imagem de Miniatura
Arquivos
art_MODESTIA_Biased_Agonist_TRV027_Determinants_in_AT1R_by_Molecular_2019.PDF (973.56 KB)
Citações na Scopus
12
Tipo de produção
article
Data de publicação
2019
Editora
AMER CHEMICAL SOC
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
MODESTIA, Silvestre Massimo
TROSSINI, Gustavo Henrique Goulart
RANGEL-YAGUI, Carlota de Oliveira
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
JOURNAL OF CHEMICAL INFORMATION AND MODELING, v.59, n.2, p.797-808, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Functional selectivity is a phenomenon observed in G protein-coupled receptors in which intermediate active-state conformations are stabilized by mutations or ligand binding, resulting in different sets of signaling pathways. Peptides capable of selectively activating beta-arrestin, known as biased agonists, have already been characterized in vivo and could correspond to a new therapeutic approach for treatment of cardiovascular diseases. Despite the potential of biased agonism, the mechanism involved in selective signaling remains unclear. In this work, molecular dynamics simulations were employed to compare the conformational profile of the angiotensin II type 1 receptor (AT1R) crystal bound to angiotensin II, bound to the biased ligand TRV027, and in the apo form. Our results show that both ligands induce changes near the NPxxY motif in transmembrane domain 7 that are related to receptor activation. However, the biased ligand does not cause the rotamer toggle alternative positioning and displays an exclusive hydrogen-bonding pattern. Our work sheds light on the biased agonism mechanism and will help in the future design of novel biased agonists for AT1R.
Palavras-chave
URI
https://observatorio.fm.usp.br/handle/OPI/31137
Referências
  1. Abraham Mark James, 2015, SoftwareX, V1-2, P19, DOI 10.1016/j.softx.2015.06.001
  2. Anezo C, 2003, J PHYS CHEM B, V107, P9424, DOI 10.1021/jp0348981
  3. Aplin M, 2009, J MOL CELL CARDIOL, V46, P15, DOI 10.1016/j.yjmcc.2008.09.123
  4. Balakumar P, 2014, J MOL ENDOCRINOL, V53, pR71, DOI 10.1530/JME-14-0125
  5. Ballesteros JA, 1995, METH NEUROSCI, P366, DOI 10.1016/S1043-9471(05)80049-7
  6. BERENDSEN HJC, 1984, J CHEM PHYS, V81, P3684, DOI 10.1063/1.448118
  7. BIHOREAU C, 1993, P NATL ACAD SCI USA, V90, P5133, DOI 10.1073/pnas.90.11.5133
  8. Boerrigter G, 2011, CIRC-HEART FAIL, V4, P770, DOI 10.1161/CIRCHEARTFAILURE.111.962571
  9. Bonde MM, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0014135
  10. Bourque K, 2017, FRONT ENDOCRINOL, V8, DOI 10.3389/fendo.2017.00061
  11. Cabana J, 2015, J BIOL CHEM, V290, P15835, DOI 10.1074/jbc.M114.627356
  12. Cabana J, 2013, J BIOL CHEM, V288, P2593, DOI 10.1074/jbc.M112.395939
  13. de Gasparo M, 2000, PHARMACOL REV, V52, P415
  14. Delano W., 2010, PYMOL MOL GRAPHICS S
  15. DeWire SM, 2007, ANNU REV PHYSIOL, V69, P483, DOI 10.1146/annurev.physiol.69.022405.154749
  16. ESSMANN U, 1995, J CHEM PHYS, V103, P8577, DOI 10.1063/1.470117
  17. Fillion D, 2013, J BIOL CHEM, V288, P8187, DOI 10.1074/jbc.M112.442053
  18. Greasley PJ, 2002, MOL PHARMACOL, V61, P1025, DOI 10.1124/mol.61.5.1025
  19. Groblewski T, 1997, J BIOL CHEM, V272, P1822, DOI 10.1074/jbc.272.3.1822
  20. Hess B, 1997, J COMPUT CHEM, V18, P1463, DOI 10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.3.CO;2-L
  21. HOOVER WG, 1985, PHYS REV A, V31, P1695, DOI 10.1103/PhysRevA.31.1695
  22. HUNYADY L, 1995, J BIOL CHEM, V270, P16602, DOI 10.1074/jbc.270.28.16602
  23. Inoue Y, 1997, J HYPERTENS, V15, P703, DOI 10.1097/00004872-199715070-00001
  24. JARVIS RA, 1973, IEEE T COMPUT, VC-22, P1025, DOI 10.1109/T-C.1973.223640
  25. Jones G, 1997, J MOL BIOL, V267, P727, DOI 10.1006/jmbi.1996.0897
  26. JORGENSEN WL, 1983, J CHEM PHYS, V79, P926, DOI 10.1063/1.445869
  27. KABSCH W, 1983, BIOPOLYMERS, V22, P2577, DOI 10.1002/bip.360221211
  28. Kandt C, 2007, METHODS, V41, P475, DOI 10.1016/j.ymeth.2006.08.006
  29. Klauda JB, 2010, J PHYS CHEM B, V114, P7830, DOI 10.1021/jp101759q
  30. Lange OF, 2010, BIOPHYS J, V99, P647, DOI 10.1016/j.bpj.2010.04.062
  31. Leftowitz RJ, 2005, SCIENCE, V308, P512, DOI 10.1126/science.1109237
  32. Liu CH, 2017, NAT COMMUN, V8, DOI 10.1038/ncomms14335
  33. Lovell SC, 2003, PROTEINS, V50, P437, DOI 10.1002/prot.10286
  34. Lyubartsev AP, 2016, BBA-BIOMEMBRANES, V1858, P2483, DOI 10.1016/j.bbamem.2015.12.033
  35. MARIE J, 1994, J BIOL CHEM, V269, P20815
  36. Marti-Solano M, 2016, DRUG DISCOV TODAY, V21, P625, DOI 10.1016/j.drudis.2016.01.009
  37. Matsoukas MT, 2013, J CHEM INF MODEL, V53, P2874, DOI 10.1021/ci400400m
  38. Matsoukas MT, 2013, J CHEM INF MODEL, V53, P2798, DOI 10.1021/ci4003014
  39. Michel MC, 2018, MOL PHARMACOL, V93, P259, DOI 10.1124/mol.117.110890
  40. Miura SI, 2008, MOL ENDOCRINOL, V22, P139, DOI 10.1210/me.2007-0312
  41. Naik P, 2010, BIOORGAN MED CHEM, V18, P8418, DOI 10.1016/j.bmc.2010.10.043
  42. Nikiforovich GV, 2005, J PEPT RES, V66, P236, DOI 10.1111/j.1399-3011.2005.00293.x
  43. NOSE S, 1984, J CHEM PHYS, V81, P511, DOI 10.1063/1.447334
  44. Ohno K, 2011, BIOCHEM BIOPH RES CO, V404, P434, DOI 10.1016/j.bbrc.2010.11.139
  45. Pang PS, 2017, EUR HEART J, V38, P2364, DOI 10.1093/eurheartj/ehx196
  46. PARRINELLO M, 1982, J CHEM PHYS, V76, P2662, DOI 10.1063/1.443248
  47. Piggot TJ, 2012, J CHEM THEORY COMPUT, V8, P4593, DOI 10.1021/ct3003157
  48. Preininger AM, 2013, J MOL BIOL, V425, P2288, DOI 10.1016/j.jmb.2013.04.011
  49. Pupo AS, 2016, PHARMACOL RES, V112, P49, DOI 10.1016/j.phrs.2016.01.031
  50. Rovati GE, 2007, MOL PHARMACOL, V71, P959, DOI 10.1124/mol.106.029470
  51. SALI A, 1993, J MOL BIOL, V234, P779, DOI 10.1006/jmbi.1993.1626
  52. Santos EL, 2004, REGUL PEPTIDES, V119, P183, DOI 10.1016/j.regpep.2004.02.009
  53. Teixeira LB, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-12074-3
  54. Vanommeslaeghe K, 2010, J COMPUT CHEM, V31, P671, DOI 10.1002/jcc.21367
  55. Violin JD, 2007, TRENDS PHARMACOL SCI, V28, P416, DOI 10.1016/j.tips.2007.06.006
  56. Violin JD, 2010, J PHARMACOL EXP THER, V335, P572, DOI 10.1124/jpet.110.173005
  57. Wermuth C. G., 2015, PRACTICE MED CHEM, P73
  58. Wisler JW, 2014, CURR OPIN CELL BIOL, V27, P18, DOI 10.1016/j.ceb.2013.10.008
  59. Xie XQ, 2013, METHOD ENZYMOL, V520, P153, DOI 10.1016/B978-0-12-391861-1.00007-1
  60. YAMANO Y, 1995, J BIOL CHEM, V270, P14024, DOI 10.1074/jbc.270.23.14024
  61. Zhang HT, 2015, J BIOL CHEM, V290, P29127, DOI 10.1074/jbc.M115.689000
  62. Zhang HT, 2015, CELL, V161, P833, DOI 10.1016/j.cell.2015.04.011
  63. Zimmerman B, 2012, SCI SIGNAL, V5, DOI 10.1126/scisignal.2002522

Coleções
Artigos e Materiais de Revistas Científicas - FM/MCP
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/13
Artigos e Materiais de Revistas Científicas - ODS/03