Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
권호 표지
DOI QR코드

DOI QR Code

Virtual Screening of Penicillin-derived Inhibitors for the Metallo-β-lactamase from Bacillus cereus

  • Lee, Jong-Sun (Department of Chemistry and Biochemistry, Baylor University) ;
  • White, Ethan (Department of Chemistry and Biochemistry, Baylor University) ;
  • Kim, Sang-Gon (Department of Chemistry and Biochemistry, Baylor University) ;
  • Kim, Sung-Kun (Department of Chemistry and Biochemistry, Baylor University)
  • Received : 2010.08.30
  • Accepted : 2010.10.06
  • Published : 2010.12.20
Download PDF
⟨ Previous Next ⟩

Abstract

The metallo-$\beta$-lactamases ($M{\beta}Ls$) are clinically significant enzymes which readily hydrolyze most $\beta$-lactam antibiotics. Discovering potential inhibitors for the $M{\beta}Ls$ is an expensive, time consuming endeavor. Virtual screening can sieve out inhibitor candidates with incompatible features prior to synthesis, decreasing these costs. Using Autodock 4.0, the binding locations and energies of four previously-studied potential inhibitors and four additional compounds obtained from the National Cancer Institute (NCI) database were computationally calculated. Based on the docking models of these eight compounds, we then designed several hypothetical inhibitor structures, compounds A through F, and performed their respective docking experiments. The docking results for compound F showed that it binds to the zinc containing active sites with a lowest predicted binding energy of -6.70 kcal/mol, suggesting F is the most likely potential $M{\beta}L$ inhibitor.

Keywords

References

  1. Fisher, J. F.; Meroueh, S. O.; Mobashery, S. Chem. Rev. 2005, 105(2), 395. https://doi.org/10.1021/cr030102i
  2. Abriata, L. A.; Gonzalez, L. J.; Llarrull, L. I.; Tomatis, P. E.; Myers, W. K.; Costello, A. L.; Tierney, D. L.; Vila, A. J. Biochemistry 2008, 47(33), 8590. https://doi.org/10.1021/bi8006912
  3. Heinz, U.; Adolph, H. W. Cell. Mol. Life Sci. 2004, 61(22), 2827. https://doi.org/10.1007/s00018-004-4214-9
  4. Sykes, R. B.; Matthew, M. J. Antimicrob. Chemother. 1976, 2(2), 115. https://doi.org/10.1093/jac/2.2.115
  5. Medeiros, A. A. Br. Med. Bull. 1984, 40(1), 18.
  6. Matagne, A.; Dubus, A.; Galleni, M.; Frere, J. M. Nat. Prod. Rep. 1999, 16(1), 1. https://doi.org/10.1039/a705983c
  7. Frere, J. M.; Dubus, A.; Galleni, M.; Matagne, A.; Amicosante, G. Biochem. Soc. Trans. 1999, 27(2), 58.
  8. Page, M. I. Curr Pharm Des 1999, 5(11), 895.
  9. Hu, Z.; Periyannan, G. R.; Crowder, M. W. Anal. Biochem. 2008, 378(2), 177. https://doi.org/10.1016/j.ab.2008.04.007
  10. Jacquin, O.; Balbeur, D.; Damblon, C.; Marchot, P.; Pauw, E. De.; Roberts, G. C.; Frere, J. M.; Matagne, A. J. Mol. Biol. 2009, 392(5), 1278. https://doi.org/10.1016/j.jmb.2009.07.092
  11. Wang, Z.; Fast, W.; Valentine, A. M.; Benkovic, S. J. Curr. Opin. Chem. Biol. 1999, 3(5), 614. https://doi.org/10.1016/S1367-5931(99)00017-4
  12. Payne, D. J.; Bateson, J. H.; Gasson, B. C.; Proctor, D.; Khushi, T.; Farmer, T. H.; Tolson, D. A.; Bell, D.; Skett, P. W.; Marshall, A. C.; Reid, R.; Ghosez, L.; Combret, Y.; Marchand-Brynaert, J. Antimicrob. Agents. Chemother. 1997, 41(1), 135.
  13. Simm, A. M.; Loveridge, E. J.; Crosby, J.; Avison, M. B.; Walsh, T. R.; Bennett, P. M. Biochem. J. 2005, 387(Pt 3), 585. https://doi.org/10.1042/BJ20041542
  14. Kapetanovic, I. M. Chem. Biol. Interact. 2008, 171(2), 165. https://doi.org/10.1016/j.cbi.2006.12.006
  15. Pozzan, A. Curr. Pharm. Des. 2006, 12(17), 2099. https://doi.org/10.2174/138161206777585247
  16. Green, D. V. Prog. Med. Chem. 2003, 41, 61. https://doi.org/10.1016/S0079-6468(02)41002-8
  17. Chen, D.; Misra, M.; Sower, L.; Peterson, J. W.; Kellogg, G. E.; Schein, C. H. Bioorg. Med. Chem. 2008, 16(15), 7225. https://doi.org/10.1016/j.bmc.2008.06.036
  18. Jaganatharaja, J.; Gowthaman, R. Bioinformation 2006, 1(4), 112. https://doi.org/10.6026/97320630001112
  19. Rogers, J. P.; Beuscher, A. E. t.; Flajolet, M.; McAvoy, T.; Nairn, A. C.; Olson, A. J.; Greengard, P. J. Med. Chem. 2006, 49(5), 1658. https://doi.org/10.1021/jm051033y
  20. Cosconati, S.; Hong, J. A.; Novellino, E.; Carroll, K. S.; Goodsell, D. S.; Olson, A. J. J. Med. Chem. 2008, 51(21), 6627. https://doi.org/10.1021/jm800571m
  21. Huey, R.; Morris, G. M.; Olson, A. J.; Goodsell, D. S. J. Comput. Chem. 2007, 28(6), 1145. https://doi.org/10.1002/jcc.20634
  22. Fabiane, S. M.; Sohi, M. K.; Wan, T.; Payne, D. J.; Bateson, J. H.; Mitchell, T.; Sutton, B. J. Biochemistry 1998, 37(36), 12404. https://doi.org/10.1021/bi980506i
  23. Buynak, J. D.; Chen, H.; Vogeti, L.; Gadhachanda, V. R.; Buchanan, C. A.; Palzkill, T.; Shaw, R. W.; Spencer, J.; Walsh, T. R. Bioorg Med. Chem. Lett. 2004, 14(5), 1299. https://doi.org/10.1016/j.bmcl.2003.12.037
  24. Schuttelkopf, A. W.; van Aalten, D. M. Acta Crystallogr. D. Biol. Crystallogr. 2004, 60(Pt 8), 1355. https://doi.org/10.1107/S0907444904011679
  25. Bounaga, S.; Laws, A. P.; Galleni, M.; Page, M. I. J. Biochem. 1998, 331(Pt 3), 703.
  26. Kim, S. K. Ph.D. dissertation, Texas Tech Universtiy, USA 2002.
  27. Diaz, N.; Suarez, D.; Merz, K. M. Jr. J. Am. Chem. Soc. 2001, 123(40), 9867. https://doi.org/10.1021/ja0113246
  28. Prosperi-Meys, C.; Wouters, J.; Galleni, M.; Lamotte-Brasseur, J. Cell Mol. Life Sci. 2001, 58(14), 2136. https://doi.org/10.1007/PL00000843
  29. Gensmantel, N. P.; Proctor, P.; Page, M. I. J.C.S. Perkin 1980, II, 1725.

Cited by

  1. Mechanism Studies of Substituted Triazol-1-yl-pyrimidine Derivatives Inhibition on Mycobacterium tuberculosis Acetohydroxyacid Synthase vol.33, pp.12, 2012, https://doi.org/10.5012/bkcs.2012.33.12.4074
  2. Kinetic characterization of a slow-binding inhibitor of Bla2: thiomaltol vol.28, pp.1, 2013, https://doi.org/10.3109/14756366.2011.640632