Article (Scientific journals)
Crystal Structure of the OXA-48 β-Lactamase Reveals Mechanistic Diversity among Class D Carbapenemases
Docquier, Jean-Denis; Calderone, V.; De Luca, F. et al.
2009In Chemistry and Biology, 16 (5), p. 540-547
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Keywords :
CHEMBIO; MICROBIO; X ray crystallography; Bacterial Proteins; Catalytic Domain; Computer Simulation; Crystallography, X-Ray; Kinetics; Protein Structure, Quaternary; Acinetobacter baumannii; Enterobacteriaceae; Negibacteria
Abstract :
[en] Carbapenem-hydrolyzing class D β-lactamases (CHDLs) are enzymes found in important Gram-negative pathogens (mainly Acinetobacter baumannii and Enterobacteriaceae) that confer resistance to β-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 Å. 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 β5-β6 loop and allowed us to propose a mechanism for carbapenem hydrolysis by OXA-48. © 2009 Elsevier Ltd. All rights reserved.
Disciplines :
Microbiology
Life sciences: Multidisciplinary, general & others
Biochemistry, biophysics & molecular biology
Author, co-author :
Docquier, Jean-Denis ;  Université de Liège - ULiège > Département des sciences de la vie > Centre d'ingénierie des protéines
Calderone, V.;  Dipartimento di Chimica, Università di Siena, Siena, I-53100, Italy, Magnetic Resonance Center CERM, Università di Firenze, Sesto Fiorentino, I-50019, Italy
De Luca, F.;  Dipartimento di Biologia Molecolare, Sezione di Microbiologia, Università di Siena, Siena, I-53100, Italy
Benvenuti, M.;  Dipartimento di Chimica, Università di Siena, Siena, I-53100, Italy
Giuliani, F.;  Dipartimento di Biologia Molecolare, Sezione di Microbiologia, Università di Siena, Siena, I-53100, Italy
Bellucci, L.;  Dipartimento Farmaco-Chimico-Tecnologico, Università di Siena, Siena, I-53100, Italy
Tafi, A.;  Dipartimento Farmaco-Chimico-Tecnologico, Università di Siena, Siena, I-53100, Italy
Nordmann, P.;  Service de Bactériologie-Virologie, Hôpital de Bicêtre, Université Paris XI, Le Kremlin-Bicêtre, Paris, F-94275, France
Botta, M.;  Dipartimento Farmaco-Chimico-Tecnologico, Università di Siena, Siena, I-53100, Italy
Rossolini, G. M.;  Dipartimento di Biologia Molecolare, Sezione di Microbiologia, Università di Siena, Siena, I-53100, Italy
Mangani, S.;  Dipartimento di Chimica, Università di Siena, Siena, I-53100, Italy, Magnetic Resonance Center CERM, Università di Firenze, Sesto Fiorentino, I-50019, Italy
Language :
English
Title :
Crystal Structure of the OXA-48 β-Lactamase Reveals Mechanistic Diversity among Class D Carbapenemases
Publication date :
2009
Journal title :
Chemistry and Biology
ISSN :
1074-5521
eISSN :
1879-1301
Publisher :
Cell Press, Cambridge, United States - Massachusetts
Volume :
16
Issue :
5
Pages :
540-547
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 20 November 2020

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