Reference : The structure of the di-zinc subclass B2 metallo-beta-lactamase CphA reveals that the...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/25856
The structure of the di-zinc subclass B2 metallo-beta-lactamase CphA reveals that the second inhibitory zinc ion binds in the "histidine" site.
English
Bebrone, Carine mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
Delbrück, Heinrich [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > Institut für Molekulare Biotechnologie > Bioanlytics > >]
Kupper, Michaël [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > Institut für Molekulare Biotechnologie > Bioanalytics > >]
Schlömer, Philipp [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > Institut für Molekulare Biotechnologie > Bioanalytics > >]
Willmann, Charlotte [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > > > >]
Frère, Jean-Marie mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
Fisher, Rainer [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > > > >]
Galleni, Moreno mailto [Université de Liège - ULg > Département des sciences de la vie > Macromolécules biologiques >]
Hoffmann, Kurt [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > Institut für Molekulare Biotechnologie > Bioanalytics > >]
2009
Antimicrobial Agents and Chemotherapy
American Society for Microbiology (ASM)
Yes (verified by ORBi)
International
0066-4804
1098-6596
Washington
DC
[en] Bacteria can defend themselves against beta-lactam antibiotics through the expression of class B beta-lactamases, which cleave the beta-lactam amide bond and render the molecule harmless. There are three subclasses of class B beta-lactamases (B1, B2 and B3), all of which require Zn(2+) for activity and can bind either one or two zinc ions. Whereas the B1 and B3 metallo-beta-lactamases are most active as di-zinc enzymes, subclass B2 enzymes such as Aeromonas hydrophila CphA are inhibited by the binding of a second zinc ion. We crystallized A. hydrophila CphA in order to determine the binding site of the inhibitory zinc ion. X-ray data from zinc-saturated crystals allowed us to solve the crystal structures of the di-zinc forms of the wild-type enzyme and N220G mutant. The first zinc ion binds in the "cysteine" site, as previously determined for the mono-zinc form of the enzyme. The second zinc ion occupies a slightly modified "histidine" site, where the conserved His118 and His196 residues act as metal ligands. This atypical coordination sphere probably explains the rather high dissociation constant for the second zinc ion compared to those observed in enzymes of subclasses B1 and B3. Inhibition by the second zinc ion results from immobilization of the catalytically-important His118 and His196 residues, as well as the folding of the Gly232-Asn233 loop into a position that covers the active site.
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS
http://hdl.handle.net/2268/25856
http://aac.asm.org/cgi/reprint/AAC.00288-09v1?view=long&pmid=19651913
We acknowledge the American Society for Microbiology

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