Journal of Integrative Natural Science (통합자연과학논문집)

The Basic Science Institute Chosun University (조선대학교 기초과학연구원)
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Homology Modeling of CCR 4: Novel Therapeutic Target and Preferential Maker for Th2 Cells

  • Shalini, M. (Department of Bioinformatics, School of Bioengineering, SRM University) ;
  • Madhavan, Thirumurthy (Department of Bioinformatics, School of Bioengineering, SRM University)
  • Received : 2014.11.13
  • Accepted : 2014.12.25
  • Published : 2014.12.31
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Abstract

C-C chemokine receptor type 4 (CCR4) is a chemokine receptor with seven transmembrane helices and it belongs to the GPCR family. It plays an important role in asthma, lung disease, atopic dermatitis, allergic bronchopulmonary aspergillosis, cancer, inflammatory bowel disease, the mosquito-borne tropical diseases, such as dengue fever and allergic rhinitis. Because of its role in wide spectrum of disease processes, CCR4 is considered to be an important drug target. Three dimensional structure of the protein is essential to determine the functions. In the present study homology modeling of human CCR4 was performed based on crystal structure of CCR5 chemokine receptor. The generated models were validated using various parameters. Among the generated homology models the best one is selected based on validation result. The model can be used for performing further docking studies to identifying the critical interacting residues.

Keywords

References

  1. G. Andrews, C. Jones, and K. Wreggett, "An intracellular allosteric site for a specific class of antagonists of the CC chemokine G protein-coupled receptors CCR4 and CCR5", Mol. Pharmacol., Vol. 73, pp 855-867, 2008.
  2. J. C. Medina, "Optimization of 2-aminothiazole derivatives as CCR4 antagonists", ChemInform, Vol. 37, pp. 33, 2006.
  3. X. Wang, F. Xu, Q. Xu, H. Mahmud, J. Houze, L. Zhu, M. Akerman, G. Tonn, L. Tang, B. E. McMaster, D. J. Dairaghi, T. J. Schall, T. L. Collins, and J. C. Medina, "Optimization of 2-Aminothiazole Derivatives as CCR4 Antagonists", Bioorg. Med. Chem. Lett., Vol. 16, pp. 2800-2803, 2006. https://doi.org/10.1016/j.bmcl.2006.01.126
  4. K. Yokoyama, N. Ishikawa, S. Igarashi, N. Kawano, N. Masuda, W. Hamaguchi, S. Yamasaki, Y. Koganemaru, K. Hattori, T. Miyazaki, S.-i. Ogino, Y. Matsumoto, M. Takeuchi, and M. Ohta, "Potent and orally bioavailable CCR4 antagonists: Synthesis and structure-activity relationship study of 2-aminoquinazolines", Bioorgan. Med. Chem., Vol. 17, pp. 64-73, 2009. https://doi.org/10.1016/j.bmc.2008.11.020
  5. K. Yokoyama, N. Ishikawa, S. Igarashi, N. Kawano, N. Masuda, K. Hattori, T. Miyazaki, S.-i. Ogino, M. Orita, Y. Matsumoto, M. Takeuchi, and M. Ohta, "Potent CCR4 antagonists: Synthesis, evaluation, and docking study of 2, 4-diaminoquinazolines", Bioorgan. Med. Chem., Vol. 16, pp. 7968-7974, 2008. https://doi.org/10.1016/j.bmc.2008.07.062
  6. A. V. Purandare, H. Wan, J. E. Somerville, C. Burke, W. Vaccaro, X. Yang. K. W. McIntyre, and M. A. Poss, "Core exploration in optimization of chemokine receptor CCR4 antagonists", Bioorg. Med. Chem. Lett., Vol. 17, pp. 679-682, 2008.
  7. H. A. Flytlie, M. Hvid, E. Lindgreen, E. Kofod-Olsen, E. Petersen, A. Jorgensen, M. Deleuran, C. Vestergaard, and B. Deleuran, "Expression of MDC/CCL22 and its receptor CCR4 in rheumatoid arthritis, psoriatic arthritis and osteoarthritis", Cytokine, Vol. 49, pp. 24-29, 2010. https://doi.org/10.1016/j.cyto.2009.10.005
  8. K. Yokoyama, N. Ishikawa, S. Igarashi, N. Kawano, K. Hattori, T. Miyazaki, S.-i. Ogino, Y. Matsumoto, M. Takeuchi, and M. Ohta, "Discovery of potent CCR4 antagonists: Synthesis and structure-activity relationship study of 2,4-diaminoquinazolines", Bioorgan. Med. Chem., Vol. 16, pp. 7021-7032, 2008. https://doi.org/10.1016/j.bmc.2008.05.036
  9. A. Purandare, H. Wan, J. Somerville, C. Burke, W. Vaccaro, X. Yang, K. W. McIntyre, and M. A. Poss, "Core exploration in optimization of chemokine receptor CCR4 antagonists", Bioorg. Med. Chem. Lett., Vol. 17, pp. 679-682, 2007. https://doi.org/10.1016/j.bmcl.2006.10.091
  10. J. Bayry, E. Tartour, and D. F. Tough, "Targeting CCR4 as an emerging strategy for cancer therapy and vaccines", Trends Pharmacol. Sci., Vol. 35, pp. 163-165, 2014. https://doi.org/10.1016/j.tips.2014.02.003
  11. T. Komiya, T. Sugiyama, K. Takeda, N. Watanabe, M. Imai, M. Kokubo, N. Tokuda, H. Ochiai, H. Habashita, and S. Shibayama, "Suppressive effects of a novel CC chemokine receptor 4 antagonist on Th2 cell trafficking in ligand- and antigen-induced mouse models", Eur. J. Pharmacol., Vol. 720, pp. 335-343, 2013. https://doi.org/10.1016/j.ejphar.2013.10.006
  12. A. Honjo, H. Ogawa, M. Azuma, T. Tezuka, S. Sone, A. Biragyn, and Y. Nishioka, "Targeted reduction of $CCR4^+$ cells is sufficient to suppress allergic airway inflammation", Respiratory Investigation, Vol. 51, pp. 241-249, 2013. https://doi.org/10.1016/j.resinv.2013.04.007
  13. P. Procopiou, J. Barrett, N. Barton, M. Begg, D. Clapham, R. Copley, A. J. Ford, R. H. Graves, D. A. Hall, A. P. Hancock, A. P. Hill, H. Hobbs, S. T. Hodgson, C. Jumeaux, Y. M. L. Lacroix, A. H. Miah, K. M. L. Morriss, D. Needham, E. B. Sheriff, R. J. Slack , C. E. Smith, S. L. Sollis, and H. Staton, "Synthesis and structure-activity relationships of indazole arylsulfonamides as allosteric CC-chemokine receptor 4 antagonists", J. Med. Chem., Vol. 56, pp.1946-1960, 2013. https://doi.org/10.1021/jm301572h
  14. A. Miah, H. Abas, M. Begg, B. Marsh, D. O'Flynn, A. Ford, J. M. Percy, P. A. Procopiou, S. A. Richards, and S.-A. Rumley, "Lead identification of benzimidazolone and azabenzimidazolone arylsulfonamides as CC-chemokine receptor 4 (CCR4) antagonists", Bioorgan. Med. Chem., Vol. 22. pp. 4298-4311, 2014. https://doi.org/10.1016/j.bmc.2014.05.021
  15. S. F. Altschul, W. Gish, W. Miller, E. W. Myers, and D. J. Lipman, "Basic local alignment search tool", J. Mol. Biol., Vol. 215, pp. 403-410, 1990. https://doi.org/10.1016/S0022-2836(05)80360-2
  16. H. M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, and P. E.Bourne, "The protein data bank", Nucleic Acids Res., Vol. 28, pp. 235-242, 2000. https://doi.org/10.1093/nar/28.1.235
  17. J. D. Thompson, D. G. Higgins, and T. J. Gibson, "CLUSTAL W: improving the sensitivity of progressive equence weighting, position-specific gap penalties and weight matrix choice", Nucleic Acids Res., Vol. 22, pp. 4673-4680, 1994. https://doi.org/10.1093/nar/22.22.4673
  18. B. K. Kuntal, P. Aparoy, and P. Reddanna, "Easy Modeller: A graphical interface to Modeller", BMC Research Notes, Vol. 3, pp. 226, 2010. https://doi.org/10.1186/1756-0500-3-226
  19. N. Eswar, M. A. Marti-Renom, B. Webb, M. S. Madhusudhan, D. Eramian, M. Shen, U. Pieper, and A. Sali, "Comparative protein structure modeling with Modeller", Current Protocols in Bioinformatics, Vol. 5, pp. 1-5, 2006.
  20. R. A. Laskowski, M. W. MacArthur, D. S. Moss, and J. M. Thornton, "Procheck: a program to check the stereochemical quality of protein structures", J. Appl. Crystallogr., Vol. 26, pp. 283-291, 1993. https://doi.org/10.1107/S0021889892009944
  21. C. Colovos and T.O. Yeates, "Verification of protein structures: patterns of nonbonded atomic interactions", Protein Sci., Vol. 2, pp. 1511-1519, 1993. https://doi.org/10.1002/pro.5560020916

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