Antibiotic binding to dizinc beta-lactamase L1 from Stenotrophomonas maltophilia: SCC-DFTB/CHARMM and DFT studies.
A dizinc beta-lactamase (L1 from Stenotrophomonas maltophilia) complexed with an antibiotic compound (moxalactam) has been studied using a hybrid quantum mechanical/molecular mechanical (QM/MM) approach. The QM region is described by the self-consistent charge-density functional tight binding (SCC-DFTB) model while the MM by CHARMM. The Michaelis complex, which is constructed from a recent X-ray structure of the L1 enzyme with the hydrolyzed moxalactam, is simulated by molecular dynamics. The simulation yields valuable insights into substrate-enzyme interaction, whose implications in the enzyme catalysis are discussed. Finally, the QM/MM results are compared with a high-level density functional theory study of a truncated active-site model and the agreement provides strong support for the SCC-DFTB treatment of the QM region.
Xu
Dingguo
D
Department of Chemistry, University of New Mexico, Albuquerque, New Mexico 87131, USA.
Guo
Hua
H
Cui
Qiang
Q
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D003198:Computer Simulation; D004583:Electrons; D006859:Hydrogen / Q000737:chemistry; D006860:Hydrogen Bonding; D006878:Hydroxides / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020615:Stenotrophomonas maltophilia / Q000201:enzymology*; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism*; D001618:beta-Lactamases / Q000737:chemistry* / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D006878:Hydroxides; D006859:Hydrogen; C031356:hydroxide ion; C088032:beta-lactamase L1; D001618:beta-Lactamases; D015032:Zinc