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

MW Crowder, J Spencer, AJ Vila

Research output: Contribution to journalArticle (Academic Journal)peer-review

296 Citations (Scopus)

Abstract

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 Zn(II) ions in the active site, empowered by an unusual flexibility.
Translated title of the contributionMetallo-beta-lactamases: novel weaponry for antibiotic resistance in bacteria
Original languageEnglish
Pages (from-to)721 - 728
JournalAccounts of Chemical Research
Volume39
DOIs
Publication statusPublished - Oct 2006

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