Substrate binding to mononuclear metallo‐β‐lactamase from Bacillus cereus

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Abstract
Structure and dynamics of substrate binding (cefotaxime) to the catalytic pocket of the mononuclear zinc-β-lactamase from Bacillus cereus are investigated by molecular dynamics simulations. The calculations, which are based on the hydrogen-bond pattern recently proposed by Dal Peraro et al. (J Biol Inorg Chem 2002; 7:704–712), are carried out for both the free and the complexed enzyme. In the resting state, active site pattern and temperature B-factors are in agreement with crystallographic data. In the complexed form, cefotaxime is accommodated into a stable orientation in the catalytic pocket within the nanosecond timescale, interacting with the enzyme zinc-bound hydroxide and the surrounding loops. The β-lactam ring remains stable and very close to the hydroxide nucleophile agent, giving a stable representation of the productive enzyme-substrate complex. Proteins 2004;54:000–000.
Funding Information
  • Istituto Nazionale di Fisica della Materia
  • Agencia Nacional de Promoción Científica y Tecnológica (PICT 99-01-6616)
  • CONICET (PIP 0582/99)
  • COFIN-MURST