1X8H

The Mono-Zinc Carbapenemase CphA (N220G mutant) Shows a Zn(II)- NH2 ARG Coordination

Summary for 1X8H

• Entry DOI: 10.2210/pdb1x8h/pdb
• Related: 1X8G 1X8I
• Descriptor: Beta-lactamase, ZINC ION, CARBONATE ION, ... (6 entities in total)
• Functional Keywords: hydrolase
• Biological source: Aeromonas hydrophila
• Cellular location: Periplasm : P26918
• Total number of polymer chains: 1
• Total formula weight: 25848.64

Authors

Garau, G.,Dideberg, O. (deposition date: 2004-08-18, release date: 2004-12-28, Last modification date: 2024-05-29)

Primary citation

Garau, G.,Bebrone, C.,Anne, C.,Galleni, M.,Frere, J.M.,Dideberg, O.
A Metallo-beta-lactamase Enzyme in Action: Crystal Structures of the Monozinc Carbapenemase CphA and its Complex with Biapenem
J.Mol.Biol., 345:785-795, 2005

PubMed Abstract: 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.

PubMed: 15588826
DOI: 10.1016/j.jmb.2004.10.070

Experimental method

X-RAY DIFFRACTION (1.6 Å)