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Docking studies suggest ligand-specific δ-opioid receptor conformations

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Abstract

An automated docking procedure was used to study binding of a series of δ-selective ligands to three models of the δ-opioid receptor. These models are thought to represent the three ligand-specific receptor conformations. Docking results are in agreement with point mutation studies and suggest that different ligands—agonists and antagonists—may bind to the same binding site under different receptor conformations. Docking to different receptor models (conformations) also suggests that by changing to a receptor-specific conformation, the receptor may open or close different binding sites to other ligands.

 Ligands 5 (green) and 6 (orange) in bindingpocket BP1 of the R1 δ-opioid receptor model

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References

  1. Golstein A (1987) Trends Pharmacol Sci 8:456–459. doi:10.1016/0165-6147(87)90038-1

    Article  Google Scholar 

  2. Pasternak GW (1993) Clin Neuropharmacol 16:1–18. doi:10.1097/00002826-199302000-00001

    Article  CAS  Google Scholar 

  3. Law PY, Wong YH, Loh HH (1999) Biopolymers 51:440–455. doi:10.1002/(SICI)1097-0282(1999)51:6<440::AID-BIP6>3.0.CO;2-T

    Article  CAS  Google Scholar 

  4. Wu S, Wong MCY, Chen M, Cho CH, Wong TM (2004) J Biomed Sci 11:726–731. doi:10.1007/BF02254356

    Article  CAS  Google Scholar 

  5. Forster K, Kuno A, Solenkova N, Felix SB, Krieg T (2007) Am J Physiol Heart Circ Physiol 293:H1604–H1608. doi:10.1152/ajpheart.00418.2007

    Article  CAS  Google Scholar 

  6. Quock RM, Burkey TH, Verga E, Hosohata Y, Hosohata K, Cowell S, Slate C, Ehlert FJ, Roeske WR, Yamamura HI (1999) Pharmacol Rev 51:503–532

    CAS  Google Scholar 

  7. Satoh M, Minami M (1995) Pharmacol Ther 68:343–364. doi:10.1016/0163-7258(95)02011-X

    Article  CAS  Google Scholar 

  8. Negri L, Potenza RL, Corsi R, Melchiorri P (1991) Eur J Pharmacol 196:335–336. doi:10.1016/0014-2999(91)90450-5

    Article  CAS  Google Scholar 

  9. Sofuoglu M, Portoghese PS, Takemori AE (1991) J Pharmacol Exp Ther 257:676

    CAS  Google Scholar 

  10. Portoghese PS, Sultana M, Nagase H, Takemori AE (1992) Eur J Pharmacol 218:195–196. doi:10.1016/0014-2999(92)90167-3

    Article  CAS  Google Scholar 

  11. Buzas B, Izenwasser S, Portoghese PS, Cox BM (1994) Life Sci 54:PL101–PL106. doi:10.1016/0024-3205(94)00412-9

    Article  CAS  Google Scholar 

  12. Ho BY, Holmes BB, Zhao J, Fujimoto J (1997) Eur J Pharmacol 319:109–114. doi:10.1016/S0014-2999(96)00827-8

    Article  CAS  Google Scholar 

  13. Connor MA, Keir MJ, Henderson G (1997) Neuropharmacology 36:125–133. doi:10.1016/S0028-3908(96)00144-X

    Article  CAS  Google Scholar 

  14. Rothman RB, Mahboubi A, Bykov V, Kim CH, deCosta BR, Jacobson AE, Rice KC (1992) Peptides 13:1137–1143. doi:10.1016/0196-9781(92)90020-4

    Article  CAS  Google Scholar 

  15. Xu H, Partilla JS, deCosta BR, Rice KC, Rothman RB (1993) Peptides 14:893. doi:10.1016/0196-9781(93)90064-N

    Article  CAS  Google Scholar 

  16. Kim KW, Kim SJ, Shin BS, Choi HY (2001) Life Sci 68:1649–1656. doi:10.1016/S0024-3205(01)00962-6

    Article  CAS  Google Scholar 

  17. Xu H, Lu Y-F, Partilla JS, Pinto J, Calderon SN, Matecka D, Rice KC, Lai J, Porreca F, Anathan S, Rothman RB (1998) Peptides 19:343–350. doi:10.1016/S0196-9781(97)00294-5

    Article  CAS  Google Scholar 

  18. Allouche S, Hasbi A, Ferey V, Sola B, Jauzac P, Polastron J (2000) Biochem Pharmacol 59:915–925. doi:10.1016/S0006-2952(99)00404-9

    Article  CAS  Google Scholar 

  19. Cvejic S, Devi LA (1997) J Biol Chem 272:26959–26964. doi:10.1074/jbc.272.43.26959

    Article  CAS  Google Scholar 

  20. Ni Q, Xu H, Partilla JS, Rice KC, Matecka D, Calderon SN, Porreca F, Lai J, Schmidhammer H, Krasnig R, Rothman RB (1998) Peptides 19:1079–1090. doi:10.1016/S0196-9781(98)00046-1

    Article  CAS  Google Scholar 

  21. Cha XY, Xu H, Rice KC, Porreca F, Lai J, Ananthan S, Rothman RB (1995) Peptides 16:191–198. doi:10.1016/0196-9781(94)00182-0

    Article  CAS  Google Scholar 

  22. Maggi CA, Schwartz TW (1997) Trends Pharmacol Sci 18:351–355

    CAS  Google Scholar 

  23. Portoghese PS (2001) J Med Chem 44:2259. doi:10.1021/jm010158+

    Article  CAS  Google Scholar 

  24. McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, Solari R, Lee MG, Food SM (1998) Nature 393:333–339. doi:10.1038/30666

    Article  CAS  Google Scholar 

  25. Yasuda K, Raynor K, Kong H, Breder CD, Takeda J, Reisine T, Bell GI (1993) Proc Natl Acad Sci USA 90:6736–6740. doi:10.1073/pnas.90.14.6736

    Article  CAS  Google Scholar 

  26. Pepin M-C, Yue SY, Roberts E, Wahlestedt C, Walker P (1997) J Biol Chem 272:9260–9267. doi:10.1074/jbc.272.14.9260

    Article  CAS  Google Scholar 

  27. Valiquette M, Vu KH, Yue SY, Wahlestedt C, Walker P (1996) J Biol Chem 271:18789–18796. doi:10.1074/jbc.271.31.18789

    Article  CAS  Google Scholar 

  28. Li X, Varga EV, Stropova D, Zalewski T, Malatynska E, Knap RJ, Roeske WR, Yamamura HI (1996) Eur J Pharmacol 300:R1–R2. doi:10.1016/0014-2999(96)00098-2

    Article  CAS  Google Scholar 

  29. Meng F, Ueda Y, Hoversten MT, Thompson RC, Taylor L, Watson SJ, Akil H (1996) Eur J Pharmacol 311:285–292. doi:10.1016/0014-2999(96)00431-1

    Article  CAS  Google Scholar 

  30. Zhu J, Yin J, Law P-Y, Claude PA, Rice KC, Evans CJ, Chen C, Yu L, Liu-Chen L-Y (1996) J Biol Chem 271:1430–1434. doi:10.1074/jbc.271.3.1430

    Article  CAS  Google Scholar 

  31. Befort K, Tabbara L, Bausch S, Chavkin C, Evans C, Keiffer B (1996) Mol Pharmacol 49:216–223

    CAS  Google Scholar 

  32. Befort K, Tabbara L, Kling D, Maigret B, Kieffer BL (1996) J Biol Chem 271:10161–10168. doi:10.1074/jbc.271.17.10161

    Article  CAS  Google Scholar 

  33. Befort K, Zilliox C, Filliol D, Yue SY, Keiffer BL (1999) J Biol Chem 274:18574–18581. doi:10.1074/jbc.274.26.18574

    Article  CAS  Google Scholar 

  34. Metzger TG, Paterlini MG, Ferguson DM, Portoghese PS (2001) J Med Chem 44:857–862. doi:10.1021/jm000381r

    Article  CAS  Google Scholar 

  35. Bonner G, Meng F, Akil H (2000) Eur J Pharmacol 403:37–44. doi:10.1016/S0014-2999(00)00578-1

    Article  CAS  Google Scholar 

  36. Kong H, Raynor K, Yasuda K, Moe ST, Portoghese PS (1993) J Biol Chem 268:23055–23058

    CAS  Google Scholar 

  37. Zhu X, Chunhe W, Cheng Z, Wu Y, Zhou D, Pei G (1997) Biochem Biophys Res Commun 232:513–516. doi:10.1006/bbrc.1997.6324

    Article  CAS  Google Scholar 

  38. Cvejic S, Trapaidze N, Cyr C, Devi VA (1996) J Biol Chem 271:4073–4076. doi:10.1074/jbc.271.8.4073

    Article  CAS  Google Scholar 

  39. Wang CH, Zhou DH, Chen J, Li GE, Pei G, Chi ZQ (1997) Acta Pharmacol Sin 18:337–340

    Google Scholar 

  40. Wang C, Cheng Z, Wei Q, Chen J, Li G, Pei G, Chi Z (1998) Biochem Biophys Res Commun 249:321–324. doi:10.1006/bbrc.1998.9080

    Article  CAS  Google Scholar 

  41. Hirst RA, Smart D, Devi LA, Lambert DG (1998) J Neurochem 70:2273–2278

    CAS  Google Scholar 

  42. Meng F, Hoversten MT, Thompson RC, Taylor L, Watson SJ, Akil H (1995) J Biol Chem 270:12730–12736. doi:10.1074/jbc.270.24.14383

    Article  CAS  Google Scholar 

  43. Jutkiewicz EM, Walker NP, Folk JE, Rice KC, Portoghese PS, Woods JH, Traynor JR (2005) J Pharmacol Exp Ther 312:1314–1320. doi:10.1124/jpet.104.078741

    Article  CAS  Google Scholar 

  44. Knapp RJ, Landsman R, Waite S, Malatynska E, Varga E, Haq W, Hruby VJ, Roeske WR, Nagase H, Yamamura HI (1995) Eur J Pharmacol 291:129–134. doi:10.1016/0922-4106(95)90134-5

    Article  CAS  Google Scholar 

  45. Cheturvedi K, Jiang X, Christoffers KH, Chinen N, Bandari P, Raveglia LF, Rozoni S, Dondio G, Howells RD (2000) Brain Res Mol Brain Res 80:166–176. doi:10.1016/S0169-328X(00)00134-0

    Article  Google Scholar 

  46. Pineyro G, Archer-Lahlou E (2007) Cell Signal 19:8–19. doi:10.1016/j.cellsig.2006.05.026

    Article  CAS  Google Scholar 

  47. Fadhil I, Schmidt R, Walpole C, Carpenter KA (2004) J Biol Chem 279:21069–21077. doi:10.1074/jbc.M311468200

    Article  CAS  Google Scholar 

  48. Alloche S, Hasbi A, Ferey V, Sola B, Jauzac P, Polastron J (2000) Biochem Pharmacol 59:915–925. doi:10.1016/S0006-2952(99)00404-9

    Article  Google Scholar 

  49. Salamon Z, Hruby VJ, Tollin G, Cowell S (2002) J Pept Res 60:322–328. doi:10.1034/j.1399-3011.2002.21060.x

    Article  CAS  Google Scholar 

  50. Samama P, Cotecchia S, Costa T, Lefkowitz RJ (1993) J Biol Chem 268:4625–4636

    CAS  Google Scholar 

  51. DeLean A, Stadel JM, Lefkowitz RJ (1980) J Biol Chem 255:7108–7117

    CAS  Google Scholar 

  52. Perez DM, Karnik SS (2005) Pharmacol Rev 57:147–161. doi:10.1124/pr.57.2.2

    Article  CAS  Google Scholar 

  53. Pogozheva ID, Lomize AL, Mosberg HI (1998) Biophys J 75:612–634 www-personal.umich.edu/∼him/modeling.htm

    Article  CAS  Google Scholar 

  54. Decaillot FM, Befort K, Filliol D, Yue SY, Walker P, Kieffer BL (2003) Nat Struct Biol 10:629–636 www.pdb.org doi:10.1038/nsb950

    Article  CAS  Google Scholar 

  55. Podlogar BL, Poda GI, Demeter DA, Zhang SP, Carson JR, Nielson LA, Reitz AB, Ferguson DM (2000) Drug Des Discov 17:34–50 www.opioid.umn.Edu/strumod/html

    CAS  Google Scholar 

  56. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M (2000) Science 289:739–745. doi:10.1126/science.289.5480.739

    Article  CAS  Google Scholar 

  57. Pogozheva ID, Lomize AL, Mosberg HI (1997) Biophys J 72:1963

    Article  CAS  Google Scholar 

  58. Kawabata T (2003) MATRAS: a program for protein 3D structure comparison. Nucleic Acids Res 31:3367–3369. doi:10.1093/nar/gkg581

    Article  CAS  Google Scholar 

  59. Yeagle PL, Denis C, Choi G, Alderfer JL, Albert AD (2000) Mol Vis 6:125–131

    CAS  Google Scholar 

  60. Yeagle PL, Choi G, Albert AD (2001) Biochemistry 40:11932–11937

    Article  CAS  Google Scholar 

  61. Salom D, Lodowski DT, Stenkamp RE, Le Trong I, Golczak M, Jastrzebska B, Harris T, Ballesteros JA, Palczewski K (2006) Proc Natl Acad Sci USA 103:16123–16128. doi:10.1073/pnas.0608022103

    Article  CAS  Google Scholar 

  62. Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) J Comput Chem 19:1639–1662. doi:10.1002/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B

    Article  CAS  Google Scholar 

  63. Peng Y, Keenan SM, Zhang Q, Welsh WJ (2005) J Mol Graph Model 24:25–33. doi:10.1016/j.jmgm.2005.05.001

    Article  CAS  Google Scholar 

  64. Hypercybe, Inc. 419 Phillip St., Waterloo, ON N2L 3X2, Canada

  65. Kane BE, Svensson B, Ferguson DM (2006) AAPS J 8:E126–E137. doi:10.1208/aapsj080115

    Article  CAS  Google Scholar 

  66. Kshirsagar TA, Fang X, Portoghese PS (1998) J Med Chem 41:2657–2660. doi:10.1021/jm980209b

    Google Scholar 

  67. Raynor K, Kong H, Law S, Heerding J, Tallent M, Livingston F, Hines J, Reisine T (1995) Molecular biology of opioid receptors. In: Lee TNH (ed) NIDA Research Monograph 161

  68. Maguire PA, Loew GH (1996) Eur J Pharmacol 318:505–509. doi:10.1016/S0014-2999(96)00894-1

    Article  CAS  Google Scholar 

  69. Portoghese PS (1993) Selective nonpeptide opioid antagonists. In: Herz A (ed) Opioids, vol I. Springer, New York

    Google Scholar 

  70. Lai J, Blisky EJ, Rothman RB, Porreca F (1994) Neuroreport 5:1049–1052

    Article  CAS  Google Scholar 

  71. Boom DC, Nitsche JF, Pintar JE, Rice KC, Woods JH, Traynor JR (2002) J Pharmacol Exp Ther 303(2):723–729. doi:10.1124/jpet.102.036525

    Article  CAS  Google Scholar 

  72. Rawls SM, Hawson JM, Inan S, Cowan A (2005) Brain Res 1049:61–69. doi:10.1016/j.brainres.2005.04.074

    Article  CAS  Google Scholar 

  73. Saitoh A, Yoshikawa Y, Onodera K, Kamei J (2005) Psychopharmacology 182(3):327–334. doi:10.1007/s00213-005-0112-6

    Article  CAS  Google Scholar 

  74. Farreus DL, Altenbach C, Yang K, Habbell WL, Khorana HG (1996) Science 274:768–770. doi:10.1126/science.274.5288.768

    Article  Google Scholar 

  75. Decaillot FM, Befort K, Filliol D, Yue S, Walker P, Kieffer BL (2003) Nat Struct Biol 10:629–636. doi:10.1038/nsb950

    Article  CAS  Google Scholar 

  76. Knapp RJ, Santoro G, DeLeon IA, Lee KB, Edsall SA, Waite S, Malatynska E, Varga E, Calderon SN, Rice KC, Rothman RB, Porreca F, Roeske WR, Yamamura HI (1996) J Pharmacol Exp Ther 277:1284–1291

    CAS  Google Scholar 

  77. Jutkiewicz EM, Eller EB, Folk JE, Rice KC, Traynor JR, Woods JH (2004) J Pharmacol Exp Ther 309:173–181. doi:10.1124/jpet.103.061242

    Article  CAS  Google Scholar 

  78. Portoghese PS, Moe ST, Takemori AE (1993) J Med Chem 36:2572–2574. doi:10.1021/jm00069a017

    Article  CAS  Google Scholar 

  79. Zhu J, Yin J, Law P-Y, Claude PA, Rice KC, Evans CJ, Chen C, Yu L, Liu-Chen L-Y (1996) J Biol Chem 271:1430–1434. doi:10.1074/jbc.271.3.1430

    Article  CAS  Google Scholar 

  80. Bi-Yi C, Wen-Qiou J, Jie C, Xin-Jian C, You-Cheng Z, Zhi-Qiong C (1999) Life Sci 65:1589–1595. doi:10.1016/S0024-3205(99)00404-X

    Article  CAS  Google Scholar 

  81. Bishop MJ, Garrido DM, Boswell GE, Collins MA, Harris PA, McNutt RW, O’Neill SJ, Wei K, Chang K-J (2003) J Med Chem 46:623–633. doi:10.1021/jm020395s

    Article  CAS  Google Scholar 

  82. Clayson J, Jales A, Tyacke RJ, Hudson AL, Nutt DJ, Lewis JW, Husbands SM (2001) Bioorg Med Chem Lett 11:939–943. doi:10.1016/S0960-894X(01)00112-3

    Article  CAS  Google Scholar 

  83. Calderon SN, Rice KC, Rothman RB, Porreca F, Flippen-Anderson JL, Kayakiri H, Xu H, Becketts K, Smith LE, Bilsky EJ, Davis P, Horvath R (1997) J Med Chem 40:695–704. doi:10.1021/jm960319n

    Article  CAS  Google Scholar 

  84. Portoghese PS, Sultana M, Moe ST, Takemori AE (1994) J Med Chem 37:579–585. doi:10.1021/jm00031a006

    Article  CAS  Google Scholar 

  85. Dondio G, Ronzoni S, Eggleston DS, Artico M, Petrillo P, Petrone G, Visenti L, Farina C, Vecchieti V, Clarke GD (1997) J Med Chem 40:3192–3198. doi:10.1021/jm9608218

    Article  CAS  Google Scholar 

  86. Jacobson AE (1998) http://www.cpdd.vcu.edu/DEC_ARCHIVES/DEC/acrobat/ DEC 1998.pdf

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Acknowledgment

This work was supported by the Ministry of Science and Environmental Protection of the Republic of Serbia.

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Authors and Affiliations

  1. Institute for General and Physical Chemistry, Belgrade, Serbia

    Vuk Micovic

  2. Faculty of Chemistry, University of Belgrade, P.O. Box 158, 11000, Belgrade, Serbia

    Milovan D. Ivanovic & Ljiljana Dosen-Micovic

  3. Centre for Chemistry, ICTM Belgrade, Belgrade, Serbia

    Ljiljana Dosen-Micovic

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  1. Vuk Micovic
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Micovic, V., Ivanovic, M.D. & Dosen-Micovic, L. Docking studies suggest ligand-specific δ-opioid receptor conformations. J Mol Model 15, 267–280 (2009). https://doi.org/10.1007/s00894-008-0396-7

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