Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/5603
Title: Crystal structure of the OXA-48 beta-lactamase reveals mechanistic diversity among class D carbapenemases.
Authors: Docquier, JEAN DENIS
Calderone, V
DE LUCA, Filomena
Benvenuti, Manuela 
Giuliani, F
Bellucci, L
Tafi, Andrea 
Nordmann, P
Botta, Maurizio 
Rossolini, GIAN MARIA
Mangani, Stefano 
Keywords: Antimicrobial resistance; beta-lactamases; carbapenemases; X-ray protein crystallography; protein structure and function
Issue Date: 2009
Project: None 
Journal: CHEMISTRY & BIOLOGY
Abstract: 
Carbapenem-hydrolyzing class D beta-lactamases (CHDLs) are enzymes found in important Gram-negative pathogens (mainly Acinetobacter baumannii and Enterobacteriaceae) that confer resistance to beta-lactam antibiotics, and notably carbapenems. The crystal structure of the OXA-48 carbapenemase was determined at pH 7.5 and at a resolution of 1.9 A. Surprisingly, and by contrast with OXA-24, the only other CHDL of known crystal structure, the structure of OXA-48 was similar to OXA-10, an enzyme devoid of carbapenemase activity, indicating that the hydrolysis of these compounds could depend on subtle changes in the active site region. Moreover, the active site groove of OXA-48 was different from that of OXA-24 in shape, dimensions, and charge distribution. Molecular dynamics pointed to the functional relevance of residues located in or close to the beta5-beta6 loop and allowed us to propose a mechanism for carbapenem hydrolysis by OXA-48.
Description: 
40773
URI: http://hdl.handle.net/20.500.12779/5603
ISSN: 1074-5521
DOI: 10.1016/j.chembiol.2009.04.010
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