Ab initio QM/MM study of class A beta-lactamase acylation: dual participation of Glu166 and Lys73 in a concerted base promotion of Ser70.

@article{Meroueh2005AbIQ,
  title={Ab initio QM/MM study of class A beta-lactamase acylation: dual participation of Glu166 and Lys73 in a concerted base promotion of Ser70.},
  author={Samy O. Meroueh and Jed F Fisher and H. Bernhard Schlegel and Shahriar Mobashery},
  journal={Journal of the American Chemical Society},
  year={2005},
  volume={127 44},
  pages={15397-407}
}
Beta-lactamase acquisition is the most prevalent basis for Gram-negative bacteria resistance to the beta-lactam antibiotics. The mechanism used by the most common class A Gram-negative beta-lactamases is serine acylation followed by hydrolytic deacylation, destroying the beta-lactam. The ab initio quantum mechanical/molecular mechanical (QM/MM) calculations, augmented by extensive molecular dynamics simulations reported herein, describe the serine acylation mechanism for the class A TEM-1 beta… CONTINUE READING