Structure of ADC-68, a novel carbapenem-hydrolyzing class C extended-spectrum β-lactamase isolated from Acinetobacter baumannii - PubMed (original) (raw)
. 2014 Nov;70(Pt 11):2924-36.
doi: 10.1107/S1399004714019543. Epub 2014 Oct 23.
Affiliations
- PMID: 25372683
- DOI: 10.1107/S1399004714019543
Structure of ADC-68, a novel carbapenem-hydrolyzing class C extended-spectrum β-lactamase isolated from Acinetobacter baumannii
Jeong Ho Jeon et al. Acta Crystallogr D Biol Crystallogr. 2014 Nov.
Abstract
Outbreaks of multidrug-resistant bacterial infections have become more frequent worldwide owing to the emergence of several different classes of β-lactamases. In this study, the molecular, biochemical and structural characteristics of an Acinetobacter-derived cephalosporinase (ADC)-type class C β-lactamase, ADC-68, isolated from the carbapenem-resistant A. baumannii D015 were investigated. The blaADC-68 gene which encodes ADC-68 was confirmed to exist on the chromosome via Southern blot analysis and draft genome sequencing. The catalytic kinetics of β-lactams and their MICs (minimum inhibitory concentrations) for A. baumannii D015 and purified ADC-68 (a carbapenemase obtained from this strain) were assessed: the strain was resistant to penicillins, narrow-spectrum and extended-spectrum cephalosporins, and carbapenems, which were hydrolyzed by ADC-68. The crystal structure of ADC-68 was determined at a resolution of 1.8 Å. The structure of ADC-68 was compared with that of ADC-1 (a non-carbapenemase); differences were found in the central part of the Ω-loop and the C-loop constituting the edge of the R1 and R2 subsites and are close to the catalytic serine residue Ser66. The ADC-68 C-loop was stabilized in the open conformation of the upper R2 subsite and could better accommodate carbapenems with larger R2 side chains. Furthermore, a wide-open conformation of the R2-loop allowed ADC-68 to bind to and hydrolyze extended-spectrum cephalosporins. Therefore, ADC-68 had enhanced catalytic efficiency against these clinically important β-lactams (extended-spectrum cephalosporins and carbapenems). ADC-68 is the first reported enzyme among the chromosomal class C β-lactamases to possess class C extended-spectrum β-lactamase and carbapenemase activities.
Keywords: Acinetobacter baumannii; carbapenemase; extended-spectrum β-lactamases (ESBLs).
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