Download MendeleyStructure of ADC-68, a novel carbapenem-hydrolyzing class C extended-spectrum beta-lactamase isolated from Acinetobacter baumannii
Jeon, J.H., Hong, M.K., Lee, J.H., Lee, J.J., Park, K.S., Karim, A.M., Jo, J.Y., Kim, J.H., Ko, K.S., Kang, L.W., Lee, S.H.(2014) Acta Crystallogr D Biol Crystallogr 70: 2924-2936
- PubMed: 25372683
- DOI: https://doi.org/10.1107/S1399004714019543
- Primary Citation of Related Structures:
4QD4 - PubMed 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.
Organizational Affiliation:
National Leading Research Laboratory of Drug Resistance Proteomics, Department of Biological Sciences, Myongji University, 116 Myongjiro, Yongin, Gyeonggido 449-728, Republic of Korea.
