Structures of the class D carbapenemase OXA-24 from Acinetobacter baumannii in complex with doripenem.

ABSTRACT: The emergence of class D β-lactamases with carbapenemase activity presents an enormous challenge to health practitioners, particularly with regard to the treatment of infections caused by Gram-negative pathogens such as Acinetobacter baumannii. Unfortunately, class D β-lactamases with carbapenemase activity are resistant to β-lactamase inhibitors. To better understand the details of the how these enzymes bind and hydrolyze carbapenems, we have determined the structures of two deacylation-deficient variants (K84D and V130D) of the class D carbapenemase OXA-24 with doripenem bound as a covalent acyl-enzyme intermediate. Doripenem adopts essentially the same configuration in both OXA-24 variant structures, but varies significantly when compared to the non-carbapenemase class D member OXA-1/do

SUBMITTER: Schneider KD 

PROVIDER: S-EPMC3057435 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature