TY  - JOUR
AU  - Docquier, J. D.
AU  - Calderone, V.
AU  - De Luca, F.
AU  - Benvenuti, M.
AU  - Giuliani, F.
AU  - Bellucci, L.
AU  - Tafi, A.
AU  - Nordmann, P.
AU  - Botta, M.
AU  - Rossolini, G. M.
AU  - Mangani, S.
AU  - DESY
TI  - Crystal structure of the OXA-48 beta-lactamase reveals mechanistic diversity among class D carbapenemases.
JO  - Chemistry & biology
VL  - 16
SN  - 1074-5521
CY  - Amsterdam [u.a.]
PB  - Cell Press
M1  - PHPPUBDB-20354
SP  - 540-547
PY  - 2009
N1  - (c) Elsevier Ltd; Open Archive
AB  - 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.
KW  - Bacterial Proteins: chemistry
KW  - Bacterial Proteins: classification
KW  - Catalytic Domain
KW  - Computer Simulation
KW  - Crystallography, X-Ray
KW  - Kinetics
KW  - Protein Structure, Quaternary
KW  - beta-Lactamases: chemistry
KW  - beta-Lactamases: classification
KW  - Bacterial Proteins (NLM Chemicals)
KW  - beta-Lactamases (NLM Chemicals)
KW  - carbapenemase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:19477418
UR  - <Go to ISI:>//WOS:000266620800009
DO  - DOI:10.1016/j.chembiol.2009.04.010
UR  - https://bib-pubdb1.desy.de/record/95357
ER  -