Molecular evolution and binding free energy analysis on substrates of KPC carbapenemases
10.3760/cma.j.issn.1674-2397.2010.03.002
- VernacularTitle:KPC型碳青霉烯酶分子进化及与底物结合自由能分析
- Author:
Zuhuang MI
;
Xingbei WENG
;
Ling QIN
- Publication Type:Journal Article
- Keywords:
Evolution,molecular;
Carbapenemase;
Molecular docking;
β-lactam;
Binding free energy
- From:
Chinese Journal of Clinical Infectious Diseases
2010;3(3):134-137
- CountryChina
- Language:Chinese
-
Abstract:
Objective To analyze molecular evolution and binding free energies in substrates of KPC-2,KPC-5 and KPC-10 carbapenemases.Methods Minimum Evolution method in MEGA 4.1 was used to analyze molecular evolution of KPC-2,KPC-5 and KPC-10 carbapenemases,Dock module in ArgusLab 4.1 was used to perform molecular docking of these 3 carbapenemases to 10 kinds of β-lactams substrates,and calculate binding free energies(△G).Results Ambler Class A β-lactamases with carbapenemase activities were grouped in the same cluster and had good conservation,while ordinary Ambler Class A β-lactamases without carbapenemase activities were groupod in the other cluster.Binding free energies of KPC-2,KPC-5 and KPC-10 carbapenemases were lower to carbapenem antibiotics than the thirdgeneration cephalosporins,while binding free energies to aztreonam and clavulanic acid were of comparatively higher levels.Conclusion Catalytic activities of KPC to carbapenem antibiotics are higher than those to the third-generation cephalosporins,but the activities to aztreonam and clavulanic acid are low.
