8EK9

Crystal structure of the class A carbapenemase CRH-1 in complex with avibactam at 1.4 Angstrom resolution

Summary for 8EK9

• Entry DOI: 10.2210/pdb8ek9/pdb
• Descriptor: Beta-lactamase, (2S,5R)-1-formyl-5-[(sulfooxy)amino]piperidine-2-carboxamide (3 entities in total)
• Functional Keywords: class a carbapenemase, environmental lactamase, chromobacterium, dbo inhibitor, antimicrobial protein
• Biological source: Chromobacterium haemolyticum
• Total number of polymer chains: 1
• Total formula weight: 28952.84

Authors

Power, P.,Brunetti, F.,Ghiglione, B.,Guardabassi, L.,Gutkind, G.,Klinke, S. (deposition date: 2022-09-20, release date: 2023-05-31, Last modification date: 2024-10-16)

Primary citation

Brunetti, F.,Ghiglione, B.,Gudeta, D.D.,Gutkind, G.,Guardabassi, L.,Klinke, S.,Power, P.
Biochemical and Structural Characterization of CRH-1, a Carbapenemase from Chromobacterium haemolyticum Related to KPC beta-Lactamases.
Antimicrob.Agents Chemother., 67:e0006123-e0006123, 2023

PubMed Abstract: KPC-2 is one of the most relevant serine-carbapenemases among the carbapenem-resistant We previously isolated from the environmental species Chromobacterium haemolyticum a class A CRH-1 β-lactamase displaying 69% amino acid sequence identity with KPC-2. The objective of this study was to analyze the kinetic behavior and crystallographic structure of this β-lactamase. Our results showed that CRH-1 can hydrolyze penicillins, cephalosporins (except ceftazidime), and carbapenems with similar efficacy compared to KPC-2. Inhibition kinetics showed that CRH-1 is not well inhibited by clavulanic acid, in contrast to efficient inhibition by avibactam (AVI). The high-resolution crystal of the apoenzyme showed that CRH-1 has a similar folding compared to other class A β-lactamases. The CRH-1/AVI complex showed that AVI adopts a chair conformation, stabilized by hydrogen bonds to Ser70, Ser237, Asn132, and Thr235. Our findings highlight the biochemical and structural similarities of CRH-1 and KPC-2 and the potential clinical impact of this carbapenemase in the event of recruitment by pathogenic bacterial species.

PubMed: 37272821
DOI: 10.1128/aac.00061-23

Experimental method

X-RAY DIFFRACTION (1.4 Å)