Citation: LIN Ke-Jiang, ZHU Dong-Ji, LENG Yong-Gan, YOU Qi-Dong. Structural Characterization of Human Parathyroid Hormone 1 Receptor[J]. Acta Physico-Chimica Sinica, ;2012, 28(07): 1783-1789. doi: 10.3866/PKU.WHXB201204192 shu

Structural Characterization of Human Parathyroid Hormone 1 Receptor

1.
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, P. R. China

Received Date: 22 February 2012
Available Online: 19 April 2012

Parathyroid hormone 1 receptor (PTH1R) is a member of the class B G-protein coupled receptor (B-GPCR) family and is involved in bone formation. Its substrate parathyroid hormone (PTH) and its analogues are being developed as anti-osteoporosis therapeutics. The structure-based rational drug design of PTH1R substrates has been hampered by the lack of experimentally determined three-dimensional (3D) structures from techniques such as nuclear magnetic resonance (NMR) and X-ray crystallography. Here, we have constructed a 3D model of PTH1R including its extracellular domain (ECD), transmembrane domain (TM) and other domains using a homology modeling approach. In addition, to capture the ligand-receptor interactions, we have manually docked human parathyroid hormone (1-34) into the top scoring receptor model, and subjected the PTH-PTH1R complex to an unconstrained energy minimization. The integral 3D receptor model provides an easier way to understand the interactions involved at the TM, ECD, and other domains. Furthermore, the parameters of hydrogen bonding, hydrophobic, and other interactions from the ligand-receptor model, enabled us to elucidate the important interactions between PTH (1-34) and PTH1R. This ligand-receptor model could potentially serve as a tool for structure-based virtual screening in the development of non-peptide based anti-osteoporosis drugs.
- Parathyroid hormone 1 receptor,
- Parathyroid hormone,
- Homology modeling,
- PTH-PTH1R complex
1. [1]
  
  (1) Potts, J. T.; Gardella, T. J. Annals of the New York Academy of Sciences 2007, 1117, 196. doi: 10.1196/annals.1402.088
2. [2]
  (2) Potts, J. T. J. Endocrinol. 2005, 187, 311. doi: 10.1677/joe.1.06057
3. [3]
  (3) Murray, T. M.; Rao, L. G.; Divieti, P.; Bringhurst, F. R. Endocr. Rev. 2005, 26, 78. doi: 10.1210/er.2003-0024
4. [4]
  (4) Gardella, T. J.; Juppner, H. Trends Endocrinol. Metab. 2001, 12,210. doi: 10.1016/S1043-2760(01)00409-X
5. [5]
  (5) Juppner, H.; Abou-Samra, A. B.; Freeman, M.; Kong, X. F.;Schipani, E.; Richards, J.; Kolakowski, L. F., Jr.; Hock, J.; Potts,J. T., Jr.; Kronenberg, H. M. Science 1991, 254, 1024. doi: 10.1126/science.1658941
6. [6]
  (6) Pioszak, A. A.; Harikumar, K. G.; Parker, N. R.; Miller, L. J.;Xu, H. E. J. Biol. Chem. 2010, 285, 12435. doi: 10.1074/jbc.M109.093138
7. [7]
  (7) Pioszak, A. A.; Xu, H. E. Proc. Natl. Acad. Sci. U. S. A. 2008,105, 5034. doi: 10.1073/pnas.0801027105
8. [8]
  (8) Jin, L.; Briggs, S. L.; Chandrasekhar, S.; Chirgadze, N. Y.;Clawson, D. K.; Schevitz, R.W.; Smiley, D. L.; Tashjian, A. H.;Zhang, F. J. Biol. Chem. 2000, 275, 27238.
9. [9]
  (9) Rolz, C.; Pellegrini, M.; Mierke, D. F. Biochemistry 1999, 38,6397. doi: 10.1021/bi9829276
10. [10]
  (10) Discovery Studio, 2.5; Accelrys Software Inc.: San Die , US,2010.
11. [11]
  (11) Pellegrini, M.; Bisello, A.; Rosenblatt, M.; Chorev, M.; Mierke,D. F. Biochemistry 1998, 37, 12737. doi: 10.1021/bi981265h
12. [12]
  (12) Cherezov, V.; Rosenbaum, D. M.; Hanson, M. A.; Rasmussen,S. G.; Thian, F. S.; Kobilka, T. S.; Choi, H. J.; Kuhn, P.;Weis,W. I.; Kobilka, B. K.; Stevens, R. C. Science 2007, 318, 1258.doi: 10.1126/science.1150577
13. [13]
  (13) Kerfeld, C. A.; Anwar, H. P.; Interrante, R.; Merchant, S.;Yeates, T. O. J. Mol. Biol. 1995, 250, 627. doi: 10.1006/jmbi.1995.0404
14. [14]
  (14) Thompson, J. D.; Higgins, D. G.; Gibson, T. J. Nucleic Acids Res. 1994, 22, 4673. doi: 10.1093/nar/22.22.4673
15. [15]
  (15) Spassov, V.; Yan, L.; Szalma, S. J. Phys. Chem. B 2002, 106,8726. doi: 10.1021/jp020674r
16. [16]
  (16) Im,W.; Lee, M. S.; Brooks, C. L. J. Comput. Chem. 2003, 24,1691. doi: 10.1002/jcc.10321
17. [17]
  (17) Luthy, R.; Bowie, J. U.; Eisenberg, D. Nature 1992, 356, 83.doi: 10.1038/356083a0
18. [18]
  (18) Lovell, S. C.; Davis, I.W.; Arendall,W. B., III; de Bakker, P. I.;Word, J. M.; Prisant, M. G.; Richardson, J. S.; Richardson, D.C. Proteins 2003, 50, 437. doi: 10.1002/prot.10286
19. [19]
  (19) Adams, A. E.; Bisello, A.; Chorev, M.; Rosenblatt, M.; Suva, L.J. Mol. Endocrinol. 1998, 12, 1673. doi: 10.1210/me.12.11.1673
20. [20]
  (20) Fletcher, R.; Powell, M. J. D. The Computer Journal 1963, 6,163.
21. [21]
  (21) Grippo, L.; Lucidi, S. Mathematical Programming 1997, 78,375.
22. [22]
  (22) MOE, 2009; Chemical Computing Group: Montreal, Canada,2009.
23. [23]
  (23) Clark, A. M.; Labute, P. J. Chem. Inf. Model. 2007, 47, 1933.doi: 10.1021/ci7001473
24. [24]
  (24) Greenberg, Z.; Bisello, A.; Mierke, D. F.; Rosenblatt, M.;Chorev, M. Biochemistry 2000, 39, 8142. doi: 10.1021/bi000195n
25. [25]
  (25) Sali, A. Mol. Med. Today 1995, 1, 270. doi: 10.1016/S1357-4310(95)91170-7
26. [26]
  (26) Dean, T.; Khatri, A.; Potetinova, Z.;Willick, G. E.; Gardella, T.J. J. Biol. Chem. 2006, 281, 32485. doi: 10.1074/jbc.M606179200
27. [27]
  (27) Barbier, J. R.; Gardella, T. J.; Dean, T.; MacLean, S.;Potetinova, Z.; Whitfield, J. F.;Willick, G. E. J. Biol. Chem.2005, 280, 23771. doi: 10.1074/jbc.M500817200
28. [28]
  (28) Mierke, D. F.; Maretto, S.; Schievano, E.; DeLuca, D.; Bisello,A.; Mammi, S.; Rosenblatt, M.; Peggion, E.; Chorev, M.Biochemistry 1997, 36, 10372. doi: 10.1021/bi970771o
29. [29]
  (29) Caporale, A.; Biondi, B.; Schievano, E.;Wittelsberger, A.;Mammi, S.; Peggion, E. Eur. J. Pharmacol. 2009, 611, 1. doi: 10.1016/j.ejphar.2009.03.040
30. [30]
  (30) Pioszak, A. A.; Parker, N. R.; Gardella, T. J.; Xu, H. E. J. Biol. Chem. 2009, 284, 28382. doi: 10.1074/jbc.M109.022905
31. [31]
  (31) Piserchio, A.; Bisello, A.; Rosenblatt, M.; Chorev, M.; Mierke,D. F. Biochemistry 2000, 39, 8153. doi: 10.1021/bi000196f
32. [32]
  (32) Hoare, S. R. Drug Discov. Today 2005, 10, 417. doi: 10.1016/S1359-6446(05)03370-2
33. [33]
  (33) Mierke, D. F.; Mao, L.; Pellegrini, M.; Piserchio, A.; Plati, J.;Tsomaia, N. Biochem. Soc. Trans. 2007, 35, 721. doi: 10.1042/BST0350721
34. [34]
  (34) Rolz, C.; Mierke, D. F. Biophys. Chem. 2001, 89, 119. doi: 10.1016/S0301-4622(00)00222-2
35. [35]
  (35) Barbier, J. R.; MacLean, S.; Whitfield, J. F.; Morley, P.;Willick,G. E. Biochemistry 2001, 40, 8955. doi: 10.1021/bi010460k
36. [36]
  (36) Luck, M. D.; Carter, P. H.; Gardella, T. J. Mol. Endocrinol.1999, 13, 670. doi: 10.1210/me.13.5.670
37. [37]
  (37) Gardella, T. J.; Juppner, H.;Wilson, A. K.; Keutmann, H. T.;Abou-Samra, A. B.; Segre, G. V.; Bringhurst, F. R.; Potts, J. T.,Jr.; Nussbaum, S. R.; Kronenberg, H. M. Endocrinology 1994,135, 1186. doi: 10.1210/en.135.3.1186
38. [38]
  (38) Bisello, A.; Adams, A. E.; Mierke, D. F.; Pellegrini, M.;Rosenblatt, M.; Suva, L. J.; Chorev, M. J. Biol. Chem. 1998,273, 22498. doi: 10.1074/jbc.273.35.22498
39. [39]
  (39) Monticelli, L.; Mammi, S.; Mierke, D. F. Biophys. Chem. 2002,95, 165. doi: 10.1016/S0301-4622(02)00005-4
40. [40]
  (40) Gensure, R. C.; Shimizu, N.; Tsang, J.; Gardella, T. J. Mol. Endocrinol. 2003, 17, 2647. doi: 10.1210/me.2003-0275
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