4QD4

Structure of ADC-68, a Novel Carbapenem-Hydrolyzing Class C Extended-Spectrum -Lactamase from Acinetobacter baumannii

Summary for 4QD4

• Entry DOI: 10.2210/pdb4qd4/pdb
• Descriptor: Beta-lactamase ADC-68, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, CITRIC ACID, ... (4 entities in total)
• Functional Keywords: beta-lactamase, hydrolase-hydrolase inhibitor complex, hydrolase
• Biological source: Acinetobacter baumannii
• Total number of polymer chains: 2
• Total formula weight: 82159.57

Authors

Hong, M.K.,Kang, L.W. (deposition date: 2014-05-13, release date: 2015-01-21, Last modification date: 2024-03-20)

Primary citation

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.
Structure of ADC-68, a novel carbapenem-hydrolyzing class C extended-spectrum beta-lactamase isolated from Acinetobacter baumannii
Acta Crystallogr.,Sect.D, 70:2924-2936, 2014

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.

PubMed: 25372683
DOI: 10.1107/S1399004714019543

Experimental method

X-RAY DIFFRACTION (1.8 Å)