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M. G. Khrenova, A. M. Kulakova, B. L. Grigorenko, A. V. Nemukhin
Mechanism of
metallo-β-lactamase inhibition by oxacephalosporin antibiotic
Abstract
Metallo-β-lactamase is a family of bacterial
zinc dependent enzymes that hydrolyzes β-lactam antibiotics and is responsible for the drug
resistance of bacteria. The slowly hydrolyzed substrate moxalactam undergoes
chemical transformations comprising not only the C-N bond cleavage, but also
release of the 1-methyltetrazolyl-5-thiolate anion. This results in the
formation of an intermediate firmly bound to the active site. In this paper we present
the results of the calculations applying the combined quantum mechanics
molecular mechanics approach, which describe the molecular mechanism of this
process.
Key words: enzyme catalysis, bacterial resistance, moxalactam, antibiotics.
Copyright (C) Chemistry Dept., Moscow State University, 2002
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