Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Comparative Homology Modeling and Ligand Docking Study of Human Catechol-O-Methyltransferase for Antiparkinson Drug Design

  • Lee, Jee-Young (Department of Chemistry and Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Yang-Mee (Department of Chemistry and Bio/Molecular Informatics Center, Konkuk University)
  • Published : 2005.11.20
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Abstract

Catechol-O-methyltransferase (COMT, EC 2.1.1.6) is an S-adenosylmethionine (SAM, AdoMet) dependent methyltransferase, and is related to the functions of the neurotransmitters in various mental processes, such as Parkinson’s disease. COMT inhibitors represent a new class of antiparkinson drugs, when they are coadministered with levodopa. Based on x-ray structure of rat COMT (rCOMT), the three dimensional structure of human COMT (hCOMT) was constructed by comparative homology modeling using MODELLER. The catalytic site of these two proteins showed subtle differences, but these differences are important to determine the characterization of COMT inhibitor. Ligand docking study is carried out for complex of hCOMT and COMT inhibitors using AutoDock. Among fifteen inhibitors chosen from world patent, nine models were energetically favorable. The average value of heavy atomic RMSD was 1.5 $\AA$. Analysis of ligand-protein binding model implies that Arg201 on hCOMT plays important roles in the interactions with COMT inhibitors. This study may give insight to develop new ways of antiparkinson drug.

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References

  1. Zhou, Z. S.; Zhao, G.; Wan, W. Frontiers of Biotechnology & Pharmaceuticals; Science press Ltd.; 2003; vol. 2, p 256
  2. Sistla, S.; Rao, D. N. Crit. Rev. Biochem. Mol. Biol. 2004, 39, 1
  3. Mannisto, P. T.; Kaakkola, S. Pharmacol. Rev. 1999, 51, 593
  4. Zhu, B. T. Curr. Drug Metabol. 2002, 3, 321 https://doi.org/10.2174/1389200023337586
  5. Martin, J. L.; McMillan, F. M. Curr. Opin. Struc. Biol. 2002, 12, 783 https://doi.org/10.1016/S0959-440X(02)00391-3
  6. Kaakkola, S. Drugs 2000, 59, 1233 https://doi.org/10.2165/00003495-200059060-00004
  7. Sangwon, L.; Yangmee, K. Bull. Korean Chem. Soc. 2004, 25, 838 https://doi.org/10.1007/s11814-008-0139-6
  8. Nissinen, E.; Kaheinen, P.; Penttila, K. E.; Kaivola, J.; Linden, I. B. Europ. J of Pharmacol. 1997, 340, 287
  9. Offen, D.; Pane, H.; Galili-Mosberg, R.; Melamed, E. Clinic. Neuropharmacology 2001, 24, 27 https://doi.org/10.1097/00002826-200101000-00006
  10. Mannisto, P. T.; Reenila, I. Medical Hypotheses 2001, 57, 628 https://doi.org/10.1054/mehy.2001.1430
  11. Tilgmann, C.; Ulmanen, I. J. of Chromatography B 1996, 684, 147 https://doi.org/10.1016/0378-4347(96)00117-X
  12. Bonifacio, M. J.; Archer, M.; Rodrigues, M. L.; Matias, P. M.; Learmonth, D. A.; Carrondo, M. A.; Soares-Da-Silva, P. Mole. Pharmacol. 2002, 62, 795 https://doi.org/10.1124/mol.62.4.795
  13. Wilkins, M. R.; Gasteiger, E.; Bairoch, A.; Sanchez, J. C.; Williams, K. L.; Appel, R. D.; Hochstrasser, D. F. Methods Mol. Biol. 1999, 112, 531
  14. Marti-Renom, M. A.; Stuart, A.; Fiser, A.; Sanchez, R.; Melo, F.; Sali, A. Annu. Rev. Biophys. Biomol. Struct. 2000, 29, 291 https://doi.org/10.1146/annurev.biophys.29.1.291
  15. Laskowski, R. A.; MacArthur, M. W.; Moss, D. S.; Thornton, J. M. J. Appl. Cryst. 1993, 26, 283 https://doi.org/10.1107/S0021889892009944
  16. Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Belew, R. W.; Olson, A. J. J. Computational Chemistry 1998, 19, 1639 https://doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B
  17. Kabsch, W.; Sander, C. Biopolymers 1983, 22, 2577 https://doi.org/10.1002/bip.360221211
  18. Pal, D.; Chakrabarti, P. Biopolymers 2002, 63, 195 https://doi.org/10.1002/bip.10051
  19. Morris, A. L.; MacArthur, M. W.; Hutchinson, E. G.; Thornton, J. M. Proteins 1992, 12, 345-364 https://doi.org/10.1002/prot.340120407

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