Neutron and X-ray crystal structures of a perdeuterated enzyme inhibitor complex reveal the catalytic proton network of the Toho-1 β-lactamase for the acylation reaction

Stephen J. Tomanicek, Robert F. Standaert, Kevin L. Weiss, Andreas Ostermann, Tobias E. Schrader, Joseph D. Ng, Leighton Coates

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Background: Antibiotic resistance from extended-spectrum β-lactamases (ESBLs) makes infections more dangerous and difficult to treat. Results: Neutron and x-ray crystal structures were determined for an ESBL in complex with an acylation transition state analog. Conclusion: Glu-166 is implicated as the general base in the acylation reaction. Significance: Understanding the catalytic mechanism of β-lactamases will lead to improved antibiotics and β-lactamase inhibitors.

Original languageEnglish
Pages (from-to)4715-4722
Number of pages8
JournalJournal of Biological Chemistry
Volume288
Issue number7
DOIs
StatePublished - Feb 15 2013

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