Reference : A metallo-beta-lactamase enzyme in action: Crystal structures of the monozinc carbape...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/9383
A metallo-beta-lactamase enzyme in action: Crystal structures of the monozinc carbapenemase CphA and its complex with biapenem
English
Garau, Gianpiero [> > > >]
Bebrone, Carine mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
Anne, Christine [> > > >]
Galleni, Moreno mailto [Université de Liège - ULg > Département des sciences de la vie > Macromolécules biologiques >]
Frère, Jean-Marie mailto [Université de Liège - ULg > Département des sciences de la vie > Département des sciences de la vie >]
Dideberg, Otto [> > > >]
28-Jan-2005
Journal of Molecular Biology
Academic Press Ltd Elsevier Science Ltd
345
4
785-795
Yes (verified by ORBi)
International
0022-2836
London
[en] antibiotic resistance ; drug design ; enzymatic mechanism ; 3D structure ; X-ray crystallography
[en] One strategy developed by bacteria to resist the action of beta-lactam antibiotics is the expression of metallo-beta-lactamases. CphA from Aeromonas hydrophila is a member of a clinically important subclass of metallo-beta-lactamases that have only one zinc ion in their active site and for which no structure is available. The crystal structures of wild-type CphA and its N220G mutant show the structural features of the active site of this enzyme, which is modeled specifically for carbapenem hydrolysis. The structure of CphA after reaction with a carbapenem substrate, biapenem, reveals that the enzyme traps a reaction intermediate in the active site. These three X-ray structures have allowed us to propose how the enzyme recognizes carbapenems and suggest a mechanistic pathway for hydrolysis of the beta-lactam. This will be relevant for the design of metallo-beta-lactamase inhibitors as well as of antibiotics that escape their hydrolytic activity. (C) 2004 Elsevier Ltd. All rights reserved.
http://hdl.handle.net/2268/9383
http://www.elsevier.com/wps/find/journaldescription.cws_home/622890/description#description
The authors acknoledge the Journal of Molecular Biology.

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