参考文献:1. Lowy FD (2003) Antimicrobial resistance: the example of / Staphylococcus aureus. J Clin Invest 111:1265-273 CrossRef 2. Diekema DJ, Pfaller MA, Schmitz FJ et al (2001) Survey of infections due to / Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997-999. Clin Infect Dis 32:S114–S132 CrossRef 3. Mazmanian SK, Liu G, Ton-That H et al (1999) / Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall. Science 285:760-63 CrossRef 4. Paterson GK, Mitchell TJ (2004) The biology of Gram-positive sortase enzymes. Trends Microbiol 12:89-5 CrossRef 5. Ton-That H, Marraffini LA, Schneewind O (2004) Protein sorting to the cell wall envelope of Gram-positive bacteria. Mol Cell Res 1694:269-78 6. Schneewind O, Mihaylova-Petkov D, Model P (1993) Cell wall sorting signals in surface proteins of Gram-positive bacteria. EMBO J 12:4803 7. Schneewind O, Model P, Fischetti VA (1992) Sorting of protein A to the staphylococcal cell wall. Science 70:267-81 8. Navarre WW, Schneewind O (1994) Proteolytic cleavage and cell wall anchoring at the LPXTG motif of surface proteins in Gram positive bacteria. Mol Microbiol 14:115-21 CrossRef 9. Perry AM, Ton-That H, Mazmanian SK et al (2002) Anchoring of surface proteins to the cell wall of / Staphylococcus aureus III. Lipid II is an in vivo peptidoglycan substrate for sortase-catalyzed surface protein anchoring. J Biol Chem 277:16241-6248 CrossRef 10. Ruzin A, Severin A, Ritacco F et al (2002) Further evidence that a cell wall precursor [C55-MurNAc-(peptide)-GlcNAc] serves as an acceptor in a sorting reaction. J Bacteriol 184:2141-147 CrossRef 11. Strominger JL, Izaki K, Matsuhashi M et al (1967) Peptidoglycan transpeptidase and d -alanine carboxypeptidase: penicillin-sensitive enzymatic reactions. Fed Proc 26:9 12. Comfort D, Clubb RT (2004) A comparative genome analysis identifies distinct sorting pathways in Gram-positive bacteria. Infect Immun 72:2710-722 CrossRef 13. Janulczyk R, Rasmussen M (2001) Improved pattern for genome-based screening identifies novel cell wall-attached proteins in Gram-positive bacteria. Infect Immun 69:4019-026 CrossRef 14. Pallen MJ, Lam AC, Antonio M et al (2001) An embarrassment of sortases A richness of substrates? Trends Microbiol 9:97-01 CrossRef 15. Maresso AW, Schneewind O (2008) Sortase as a target of anti-infective therapy. Pharmacol Rev 60:128-41 CrossRef 16. Suree N, Jung ME, Clubb RT (2007) Recent advances towards new anti-infective agents that inhibit cell surface protein anchoring in / Staphylococcus aureus and other Gram-positive pathogens. Mini Rev Med Chem 7:991-000 CrossRef 17. Oh K-B, Nam K-W, Ahn H et al (2010) Therapeutic effect of (Z)-3-(2, 5-dimethoxyphenyl)-2-(4-methoxyphenyl) acrylonitrile (DMMA) against 〈i? / Staphylococcus aureus ?i?infection in a murine model. Biochem Biophys Res Commun 396:440-44 CrossRef 18. Chang S, Sievert DM, Hageman JC et al (2003) Infection with vancomycin-resistant / Staphylococcus aureus containing the vanA resistance gene. New Engl J Med 348:1342-347 CrossRef 19. Klevens RM, Morrison MA, Nadle J et al (2007) Invasive methicillin-resistant / Staphylococcus aureus infections in the United States. J Am Med Assoc 298:1763-771 CrossRef 20. Waldvogel FA (1999) New resistance in / Staphylococcus aureus. New Engl J Med 340:556-57 CrossRef 21. Chambers HF (2001) The changing epidemiology of / Staphylococcus aureus? Infect Dis 7:178 CrossRef 22. Talbot GH, Bradley J, Edwards JE et al (2006) Bad bugs need drugs: an update on the development pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America. Clin Infect Dis 42:657-68 CrossRef 23. Chenna BC, Shinkre BA, King JR et al (2008) Identification of novel inhibitors of bacterial surface enzyme / Staphylococcus aureus Sortase A. Bioorg Med Chem Lett 18:380-85 CrossRef 24. BABEL O (2010) OEChem v (2010) OpenEye Scientific Software, Inc. (Santa Fe, NM, USA, www.eyesopen.com) 25. MayaChemTools MayaChemTools (www.mayachemtools.org) 26. Suree N, Yi SW, Thieu W et al (2009) Discovery and structure-activity relationship analysis of / Staphylococcus aureus sortase A inhibitors. Bioorg Med Chem 17:7174-185 CrossRef 27. FRED (2010) OpenEye Scientific Software, Inc. (Santa Fe, NM, USA, www.eyesopen.com) 28. Stahl M, Rarey M (2001) Detailed analysis of scoring functions for virtual screening. J Med Chem 44:1035-042 CrossRef 29. UlHaq Z, Uddin R, Gul S (2011) Optimization of structure based virtual screening protocols against thymidine monophosphate kinase inhibitors as antitubercular agents. Mol Inf 30:851-62 CrossRef 30. McGann M (2012) FRED and HYBRID docking performance on standardized datasets. J Comput Aided Mol Des 26:897-06 CrossRef 31. McGann M (2011) FRED pose prediction and virtual screening accuracy. J Chem Inf Model 51:578-96 CrossRef 32. Pencheva T, Soumana OS, Pajeva I et al (2010) Post-docking virtual screening of diverse binding pockets: comparative study using DOCK, AMMOS, X-score and FRED scoring functions. Eur J Med Chem 45:2622-628 CrossRef 33. Zong Y, Bice TW, Ton-That H et al (2004) Crystal structures of / Staphylococcus aureus sortase A and its substrate complex. J Biol Chem 279:31383-1389 CrossRef 34. Martinez-Hackert E, Anikeeva N, Kalams SA et al (2006) Structural basis for degenerate recognition of natural HIV peptide variants by cytotoxic lymphocytes. J Biol Chem 281:20205-0212 CrossRef 35. CLCSequence (2013) CLC sequence viewer vers. 6.3 (CLC bio, Aarhus, Denmark) 36. Kitchen DB, Decornez H, Furr JR et al (2004) Docking and scoring in virtual screening for drug discovery: methods and applications. Nat Rev Drug Disc 3:935-49 CrossRef 37. Li Y, Kim DJ, Ma W et al (2011) Discovery of novel checkpoint kinase 1 inhibitors by virtual screening based on multiple crystal structures. J Chem Inf Mod 51:2904-914 CrossRef 38. Schulz-Gasch T, Stahl M (2003) Binding site characteristics in structure-based virtual screening: evaluation of current docking tools. J Mol Mod 9:47-7 39. Race PR, Bentley ML, Melvin JA et al (2009) Crystal structure of / Streptococcus pyogenes Sortase A implications for sortase mechanism. J Biol Chem 284:6924-933 CrossRef 40. Pala D, Beuming T, Sherman W et al (2013) Structure-based virtual screening of MT2 melatonin receptor: influence of template choice and structural refinement. J Chem Inf Mod 53:821-35 CrossRef
作者单位:Reaz Uddin (1) Kiran Saeed (1)
1. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
ISSN:1573-4978
文摘
Methicillin resistant Staphylococcus aureus (MRSA) is one of the challenging bacterial pathogen due to its acquired resistance to the β lactam antibiotics. The Sortase A is an enzyme of Gram-positive bacteria including S. aureus to anchor surface proteins to the cell wall. Sortase A is well studied enzyme and considered as the drug target against MRSA. Sortase A plays active role in anchoring the virulence proteins on the cell wall of the Gram-positive bacteria. The inhibition of Sortase A activity results in the separation of S. aureus from the host cells and ultimately alleviation of the infection. Here, we adapted a structure-based virtual screening protocol which helped in identification of novel potential inhibitors of Sortase A. The protocol involved the docking of a chemical library of druglike compounds with the Sortase A binding site represented by multiple crystal structures. The compounds were ranked by multiple scoring functions and shortlisted for future experimental screening. The method resulted in shortlisting of three compounds as potential novel inhibitors of Sortase A out of a large chemical library. The high rankings of shortlisted compounds estimated by multiple scoring functions showed their binding potential with Sortase A. The results are proved to be a simple yet efficient choice of structure-based virtual screening. The identified compounds are druglike and show high rankings among all set protocols of the virtual screening. We hope that the study would eventually help to expedite the discovery of novel drug candidates against MRSA.