Protonation of the beta-lactam nitrogen is the trigger event in the catalytic action of class A beta-lactamases.

ABSTRACT: The pH dependence of the pK(a) values of all ionizable groups and of the electrostatic potential at grid points corresponding to catalytically important atoms in the active site of TEM-1 beta-lactamase has been calculated by a mean-field approach for reaction intermediates modeled on the basis of energy minimized x-ray crystallographic coordinates. By estimating electrostatic contributions to the free energy changes accompanying the conversion of the free enzyme into the acylenzyme reaction intermediate, we found that acid-catalyzed protonation of the beta-lactam nitrogen is energetically favored as the initiating event, followed by base-catalyzed nucleophilic attack on the carbonyl carbon of the beta-lactam group. N-protonation is catalyzed through a hydrogen-bonded cluster involving the

SUBMITTER: Atanasov BP 

PROVIDER: S-EPMC16209 | biostudies-literature | 2000 Mar

REPOSITORIES: biostudies-literature