Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Homology Modeling and Docking Study of β-Ketoacyl Acyl Carrier Protein Synthase Ⅲ from Enterococcus Faecalis

  • Jeong, Ki-Woong (Department of Bioscience and Biotechnology, and Bio/Molecular Informatics Center, Konkuk University) ;
  • Lee, Jee-Young (Department of Bioscience and Biotechnology, and Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Yang-Mee (Department of Bioscience and Biotechnology, and Bio/Molecular Informatics Center, Konkuk University)
  • Published : 2007.08.20
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Abstract

β-Ketoacyl acyl carrier protein synthase (KAS) III is a particularly attractive target in the type II fatty acid synthetic pathway, since it is central to the initiation of fatty acid synthesis. Enterococcus faecalis, a Grampositive bacterium, is one of the major causes of hospital acquired infections. The rise of multidrug-resistant of most bacteria requires the development of new antibiotics, such as inhibition of the KAS III. In order to block the fatty acid synthesis by inhibition of KAS III, at first, three dimensional structure of Enterococcus faecalis KAS III (efKAS III) was determined by comparative homology modeling using MODELLER based on x-ray structure of Staphylococcus aureus KAS III (saKAS III) which is a gram-positive bacteria and is 36.1% identical in amino acid sequences with efKAS III. Since His-Asn-Cys catalytic triad is conserved in efKAS III and saKAS III, substrate specificity of efKAS III and saKAS III and the size of primer binding pocket of these two proteins are expected to be similar. Ligand docking study of efKAS III with naringenin and apigenin showed that naringenin docked more strongly with efKAS III than apigenin, resulting in the intensive hydrogen bond network between naringenin and efKAS III. Also, only naringenin showed antibacterial activity against E. faecalis at 256 μg/mL. This study may give practical implications of flavonoids for antimicrobial effects against E. faecalis.

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References

  1. Nie, Z.; Perretta, C.; Lu, J.; Su, Y.; Margosiak, S.; Gajiwala, K. S.; Cortez, J.; Nikulin, V.; Yager, K. M.; Appelt, K.; Chu, S. J. Med. Chem. 2004, 48, 1596 https://doi.org/10.1021/jm049141s
  2. Davies, C.; Heath, R. J.; White, S. W.; Rock, C. O. Structure 2000, 8, 185 https://doi.org/10.1016/S0969-2126(00)00094-0
  3. Khandekar, S. S.; Daines, R. A.; Lonsdale, J. T. Current Protein and Peptide Science 2003, 4, 21 https://doi.org/10.2174/1389203033380377
  4. Qiu, X.; Janson, C. A.; Smith, W. W.; Head, M.; Lonsdale, J.; Konstantinidis, A. K. J. Mol. Biol. 2001, 307, 341 https://doi.org/10.1006/jmbi.2000.4457
  5. White, S. W.; Zheng, J.; Zhang, Y. M.; Rock, C. O. Annu. Rev. Biochem. 2005, 74, 791 https://doi.org/10.1146/annurev.biochem.74.082803.133524
  6. Price, A. C.; Choi, K. H.; Heath, R. J.; Li, Z.; White, S. W.; Rock, C. O. J. Biol. Chem. 2001, 276, 6551 https://doi.org/10.1074/jbc.M007101200
  7. Payne, D. J.; Warren, P. V.; Holmes, D. J.; Ji, Y.; Lonsdale, J. T. DDT 2001, 6, 537 https://doi.org/10.1016/S1359-6446(01)01774-3
  8. Kristich, C. J.; Li, Y. H.; Cvitkovitch, D. G.; Dunny, G. M. J. Bactriology 2004, 186, 154 https://doi.org/10.1128/JB.186.1.154-163.2004
  9. Qiu, X.; Choudhry, A. E.; Janson, C. A.; Grooms, M.; Daines, R. A.; Lonsdale, J. T.; Khandekar, S. S. Protein Science 2005, 14, 2087 https://doi.org/10.1110/ps.051501605
  10. Fujita, M.; Shiota, S.; Kuroda, T.; Hatano, T.; Yoshida, T.; Mizushima, T.; Tsuchiya, T. Microbial. Immunol. 2005, 49, 391 https://doi.org/10.1111/j.1348-0421.2005.tb03732.x
  11. 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
  12. Marti-Renom, M. A.; Stuart, A.; Fiser, A.; Sanchez, R.; Melo, F.; Sali, A. Annu. Rev. Biophys. Biomol. Struct. 2000, 29, 291
  13. Lee, J. Y.; Kim, Y. M. Bull. Korean Chem. Soc. 2005, 26, 11
  14. Laskowski, R. A.; MacArthur, M. W.; Moss, D. S.; Thornton, J. M. J. Appl. Cryst. 1993, 26, 283 https://doi.org/10.1107/S0021889892009944
  15. 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
  16. Bharatham, N.; Bharatham, K.; Lee, K. W. Bull. Korean Chem. Soc. 2006, 27, 2 https://doi.org/10.5012/bkcs.2006.27.2.266
  17. Kim, P.; Zhang, Y. M.; Shenoy, G.; Nguyen, Q. A.; Boshoff, H. I.; Manjunatha, U. H.; Goodwin, M. B.; Lonsdale, J.; Price, A. C.; Miller, D. J.; Duncan, K.; White, S. W.; Rock, C. O.; Barry, C. E.; Dowd, C. S. J. Med. Chem. 2006, 49, 159 https://doi.org/10.1021/jm050825p
  18. Morris, A. L.; MacArthur, M. W.; Hutchinson, E. G.; Thornton, J. M. Proteins 1992, 12, 345 https://doi.org/10.1002/prot.340120407
  19. Pal, D.; Chakrabarti, P. Biopolymers 2002, 63, 195 https://doi.org/10.1002/bip.10051
  20. Khandekar, S. S.; Gentry, D. R.; Van Aller, G. S.; Warren, P.; Xiang, C. S.; Doyle, M. L.; Chambers, P. A.; Konstantinidis, A. K.; Brandt, M.; Daines, R. A.; Lonsdale, J. T. J. Biol. Chem. 2001, 276, 30024 https://doi.org/10.1074/jbc.M101769200
  21. Qiu, X.; Janson, C. A.; Konstantinidis, A. K.; Nwagwu, S.; Silverman, C.; Smith, W. W.; Khandekar, S.; Lonsdale, J.; Abdel-Meguid, S. S. J. of Biol. Chem. 1999, 274, 36465
  22. Narayana, K. R.; Sripal, R. M.; Chaluvaldi, M. R.; Krishna, D. R. Indian Journal of Pharmacology 2001, 33, 2
  23. Han, S. S.; Lee, C. K.; Kim, Y. S. Yakhak Hoeji. 1992, 36, 5

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