%0 Journal Article
%A Docquier, J. D.
%A Calderone, V.
%A De Luca, F.
%A Benvenuti, M.
%A Giuliani, F.
%A Bellucci, L.
%A Tafi, A.
%A Nordmann, P.
%A Botta, M.
%A Rossolini, G. M.
%A Mangani, S.
%A DESY
%T Crystal structure of the OXA-48 beta-lactamase reveals mechanistic diversity among class D carbapenemases.
%J Chemistry & biology
%V 16
%@ 1074-5521
%C Amsterdam [u.a.]
%I Cell Press
%M PHPPUBDB-20354
%P 540-547
%D 2009
%Z (c) Elsevier Ltd; Open Archive
%X 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.
%K Bacterial Proteins: chemistry
%K Bacterial Proteins: classification
%K Catalytic Domain
%K Computer Simulation
%K Crystallography, X-Ray
%K Kinetics
%K Protein Structure, Quaternary
%K beta-Lactamases: chemistry
%K beta-Lactamases: classification
%K Bacterial Proteins (NLM Chemicals)
%K beta-Lactamases (NLM Chemicals)
%K carbapenemase (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:19477418
%U <Go to ISI:>//WOS:000266620800009
%R 10.1016/j.chembiol.2009.04.010
%U https://bib-pubdb1.desy.de/record/95357