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Communication

The Acylation Mechanism of CTX-M β-Lactamase at 0.88 Å Resolution

Yu Chen,^† Richard Bonnet,^‡ and Brian K. Shoichet*^†

Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th Street, MC 2550, San Francisco, California 94158-2330, Laboratoire de Bactriologie, Centre Hospitalier Universitaire-Facult de Mdecine, 28 Place Heri-Dunant, Clermont-Ferrand Cedex, France 63001

J. Am. Chem. Soc., 2007, 129 (17), pp 5378–5380

DOI: 10.1021/ja0712064

Publication Date (Web): April 5, 2007

†

University of California San Francisco.

‡

Centre Hospitalier Universitaire-Faculté de Médecine.

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, shoichet@cgl.ucsf.edu

Abstract

The apo crystal structure of CTX-M-9 β-lactamase has been determined to 0.88 Å at pH 8.8. This unusually clear picture of proton positions and residue interactions supports the role of Glu166 as the general base for the controversial acylation step of class A β-lactamase catalysis. The ability to distinguish low-energy conformations sampled by the enzyme allows us to link the two conformations of Lys73 to different protonation states of Glu166.

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PDB: 2P74

History

Published In Issue May 02, 2007
Received February 22, 2007

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Communication

The Acylation Mechanism of CTX-M β-Lactamase at 0.88 Å Resolution