Substrate binding and catalytic mechanism of class B β-lactamases: A molecular modelling study

C. Prosperi-Meys, J. Wouters, M. Galleni, J. Lamotte-Brasseur

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs


Increased resistance to β-lactam antibiotics is mainly due to β-lactamases whose production by pathogenic bacteria makes their broad activity spectrum especially frightening. X-ray structures of several zinc β-lactamases have revealed the coordination of the two metal ions, but their mode of action remains unclear. Geometry optimisation of stable complexes along the reaction pathway of benzylpenicillin hydrolysis highlighted a proton shuttle occurring from D 120 of the Bacillus cereus β-lactamase to the β-lactam nitrogen via Zn2 which is central to the network. First, the Zn1 ion has a structural role maintaining Zn-bound waters, WAT1 and WAT2, either directly or through the Zn1 tetrahedrally coordinated histidine ligands. The Zn2 ion has a more catalytic role, stabilising the tetrahedral intermediate, accepting the β-lactam nitrogen atom as a ligand. The role of Zn2 and the flexibility in the coordination geometry of both Zn ions is of crucial importance for catalysis.

langue originaleAnglais
Pages (de - à)2136-2143
Nombre de pages8
journalCellular and Molecular Life Sciences
Numéro de publication14
Etat de la publicationPublié - 1 déc. 2001

Empreinte digitale

Examiner les sujets de recherche de « Substrate binding and catalytic mechanism of class B β-lactamases: A molecular modelling study ». Ensemble, ils forment une empreinte digitale unique.

Contient cette citation