Metallo-beta-lactamases: novel weaponry for antibiotic resistance in bacteria.

CROWDER, M.; SPENCER, J.; VILA, AJ

ACCOUNTS OF CHEMICAL RESEARCH

ACCOUNTS OF CHEMICAL RESEARCH

Lugar: Washington DC, USA; Año: 2006 vol. 39 p. 721 - 728

0001-4842

Metallo-beta-lactamases are broad-spectrum zinc enzymes, able to inactivate most clinically useful beta-lactam antibiotics. Their structural and functional diversity has thus far limited the understanding of their catalytic mechanism, therefore thwarting the rational design of a common inhibitor. On the basis of the recent availability of structures of enzyme-product complexes and novel mechanistic studies, here, we attempt to find minimal common elements in different members of this family. In contrast with other metalloenzymes, most of the substrate binding and catalytic power resides in the adequate positioning of one or two ZnII ions in the active site, empowered by an unusual flexibility.