1x8h
|
The Mono-Zinc Carbapenemase CphA (N220G mutant) Shows a Zn(II)- NH2 ARG Coordination
OverviewOverview
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.
About this StructureAbout this Structure
1X8H is a Single protein structure of sequence from Aeromonas hydrophila with ZN, CO3, SO4 and GOL as ligands. Active as Beta-lactamase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.
ReferenceReference
A metallo-beta-lactamase enzyme in action: crystal structures of the monozinc carbapenemase CphA and its complex with biapenem., Garau G, Bebrone C, Anne C, Galleni M, Frere JM, Dideberg O, J Mol Biol. 2005 Jan 28;345(4):785-95. PMID:15588826
Page seeded by OCA on Wed Nov 21 05:53:47 2007