2GKL

Crystal structure of the zinc carbapenemase CPHA in complex with the inhibitor pyridine-2,4-dicarboxylate

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.86 Å
  • R-Value Free: 0.196 
  • R-Value Work: 0.159 
  • R-Value Observed: 0.161 

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This is version 1.3 of the entry. See complete history. 


Literature

Competitive Inhibitors of the CphA Metallo-{beta}-Lactamase from Aeromonas hydrophila

Horsfall, L.E., Garau, G., Lienard, B.M.R., Dideberg, O., Schofield, C.J., Frere, J.M., Galleni, M.

(2007) Antimicrob Agents Chemother 51: 2136-2142

  • DOI: https://doi.org/10.1128/AAC.00866-06
  • Primary Citation of Related Structures:  
    2GKL

  • PubMed Abstract: 

    Various inhibitors of metallo-beta-lactamases have been reported; however, none are effective for all subgroups. Those that have been found to inhibit the enzymes of subclass B2 (catalytically active with one zinc) either contain a thiol (and show less inhibition towards this subgroup than towards the dizinc members of B1 and B3) or are inactivators behaving as substrates for the dizinc family members. The present work reveals that certain pyridine carboxylates are competitive inhibitors of CphA, a subclass B2 enzyme. X-ray crystallographic analyses demonstrate that pyridine-2,4-dicarboxylic acid chelates the zinc ion in a bidentate manner within the active site. Salts of these compounds are already available and undergoing biomedical testing for various nonrelated purposes. Pyridine carboxylates appear to be useful templates for the development of more-complex, selective, nontoxic inhibitors of subclass B2 metallo-beta-lactamases.

    • Organizational Affiliation: 

    Centre d'Ingéniérie des Protéines, Université de Liège, Allée de 6 Aout B6, Sart-Tilman, Liège, Belgium.


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-lactamase227Aeromonas hydrophilaMutation(s): 0 
Gene Names: cphA
EC: 3.5.2.6
UniProt
Find proteins for P26918 (Aeromonas hydrophila)
Explore P26918 
Go to UniProtKB:  P26918
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP26918
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.86 Å
  • R-Value Free: 0.196 
  • R-Value Work: 0.159 
  • R-Value Observed: 0.161 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.638α = 90
b = 101.211β = 90
c = 117.121γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
SCALAdata scaling
CCP4model building
REFMACrefinement
CCP4data scaling
CCP4phasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-03-13
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description