Bulletin of the Korean Chemical Society

  • 제30권8호
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  • Pages.1835-1838
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  • 2009
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  • 0253-2964(pISSN)
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  • 1229-5949(eISSN)
대한화학회 (Korean Chemical Society)
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Flavonoids can be Potent Inhibitors of Human Phenylethanolamine N-Methyltransferase (hPNMT)

  • Lee, Jee-Young (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Jeong, Ki-Woong (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Yang-Mee (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University)
  • 발행 : 2009.08.20
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초록

Inhibition of human phenylethanolamine N-methyltransferase (hPNMT) has been proposed as a method for the treatment of several mental processes which related on adrenaline metabolism. We performed in silico screening to identify flavonoid inhibitors of hPNMT using automated docking method and selected 9 inhibitor candidates based on ligand score (LigScore) and binding free energy (${\Delta}G_{bind}$) estimation. Among 9 flavonoid candidates, 7 flavonoids belong to flavones while the rest of them belong to flavanone. All candidates have common chemical features; two hydrogen bond interactions with side chain of Lys75 and backbone carbonyl oxygen of Asn39, and two hydrophobic interactions. One hydrophobic site is formed by Val53, Leu262, and Met258 and the other is made up of Phe182, Ala186, Tyr222, and Val269. This study can be helpful to understand the structural features for inhibition of PNMT and showed flavonoids as promising inhibitor candidates for hPNMT.

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참고문헌

  1. Matsubara, K.; Aoyama, K.; Suno, M.; Awaya, T. Neurotoxicol. Teratol. 2002, 24, 593 https://doi.org/10.1016/S0892-0362(02)00212-X
  2. Berecek, K. H.; Brody, M. J. Am. J. Physiol. 1982, 242, H593
  3. Martin, J. L.; Begun, J.; McLeish, M. J.; Caine, J. M.; Grunewald, G. L. Structure 2001, 9, 977 https://doi.org/10.1016/S0969-2126(01)00662-1
  4. Mefford, I. N.; Lister, R. G.; Ota, M.; Linnoila, M. Alcohol. Clin. Exp. Res. 1990, 14, 53 https://doi.org/10.1111/j.1530-0277.1990.tb00446.x
  5. Kennedy, B. P.; Bottiglieri, T.; Arning, E.; Ziegler, M. G.; Hansen, L. A.; Masliah, E. J. Neural. Transm. 2004, 111, 547 https://doi.org/10.1007/s00702-003-0096-5
  6. Krizanova, O.; Myslivecek, J.; Tillinger, A.; Jurkovicova, D.; Kubovcakova, L. Stress 2007, 10, 173 https://doi.org/10.1080/10253890701305754
  7. Comings, D. E. Ann. N Y Acad. Sci. 2001, 931, 50 https://doi.org/10.1111/j.1749-6632.2001.tb05773.x
  8. Cazarolli, L. H.; Zanatta, L.; Alberton, E. H.; Figueiredo, M. S.; Folador, P.; Damazio, R. G.; Pizzolatti, M. G.; Silva, F. R. Mini Rev. Med. Chem. 2008, 8, 1429 https://doi.org/10.2174/138955708786369564
  9. Rajnaryana, K.; Sripalreddy, M.; Chalavadi, M. R.; Krishna, D. R. Indian J. Pharmacol. 2001, 33, 2
  10. Saraf, S.; Ashawat, M. S.; Saraf, S. Phcog. Rev. 2007, 1, 30
  11. Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Belew, R. K.; 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
  12. Lee, J. Y.; Jung, K. W.; Kim, Y. Bull. Korean Chem. Soc. 2008, 29, 1717 https://doi.org/10.5012/bkcs.2008.29.9.1717
  13. Healy, E. F.; Sanders, J.; King, P. J.; Robinson, W. E., Jr. J. Mol. Graph. Model. 2009, 27, 584 https://doi.org/10.1016/j.jmgm.2008.09.011
  14. Krammer, A.; Kirchhoff, P. D.; Venkatachalam, X. J. C. M.; Waldman, M. J. Mol. Graph. Model. 2005, 23, 395 https://doi.org/10.1016/j.jmgm.2004.11.007
  15. Lee, J. Y.; Jung, K. W.; Woo, E. R.; Kim, Y. Bull. Korean Chem. Soc. 2008, 29, 1479 https://doi.org/10.5012/bkcs.2008.29.8.1479
  16. Gee, C. L.; Tyndall, J. D.; Grunewald, G. L.; Wu, Q.; McLeish, M. J.; Martin, J. L. Biochemistry 2005, 44, 16875 https://doi.org/10.1021/bi051636b
  17. Gee, C. L.; Drinkwater, N.; Tyndall, J. D.; Grunewald, G. L.; Wu, Q.; McLeish, M. J.; Martin, J. L. J. Med. Chem. 2007, 50, 4845 https://doi.org/10.1021/jm0703385
  18. Raha, K.; Merz, K. M., Jr. Calculating Binding Free Energy in Protein-ligand Interaction, in Annual Reports in Computational Chemistry; Spellmeyer, D., Ed.; Elsevier: Amsterdam, 2005; Vol. 1, p 115
  19. Grunewald, G. L.; Romero, F. A.; Criscione, K. R. J. Med. Chem. 2005, 48, 134 https://doi.org/10.1021/jm049368n
  20. Wu, Q.; Criscione, K. R.; Grunewald, G. L.; McLeish, M. J. Bioorg. Med. Chem. Lett. 2004, 14, 4217 https://doi.org/10.1016/j.bmcl.2004.06.009
  21. Coen, C. W.; Gallo, R. V. J. Endocrinol. 1986, 111, 51 https://doi.org/10.1677/joe.0.1110051

피인용 문헌

  1. Discovery of novel human phenylethanolamine N-methyltransferase (hPNMT) inhibitors using 3D pharmacophore-Based in silico, biophysical screening and enzymatic activity assays vol.29, pp.6, 2010, https://doi.org/10.1007/s10059-010-0074-3
  2. Docking Study of Flavonols and Human c-Jun N-terminal Kinase 1 vol.31, pp.8, 2009, https://doi.org/10.5012/bkcs.2010.31.8.2147
  3. Mutagenic Analysis of hPNMT Confirms the Importance of Lys57 and the Inhibitor Binding Site vol.32, pp.2, 2009, https://doi.org/10.5012/bkcs.2011.32.2.455
  4. The influence of β-cyclodextrin encapsulation on the binding of 2'-hydroxyflavanone with calf thymus DNA vol.98, pp.None, 2009, https://doi.org/10.1016/j.saa.2012.08.068