2QDS

Crystal Structure of the Zinc Carbapenemase CPHA in Complex with the Inhibitor D-Captopril


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.66 Å
  • R-Value Free: 0.170 
  • R-Value Work: 0.148 
  • R-Value Observed: 0.149 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structural basis for the broad-spectrum inhibition of metallo-beta-lactamases by thiols.

Lienard, B.M.Garau, G.Horsfall, L.Karsisiotis, A.I.Damblon, C.Lassaux, P.Papamicael, C.Roberts, G.C.Galleni, M.Dideberg, O.Frere, J.M.Schofield, C.J.

(2008) Org Biomol Chem 6: 2282-2294

  • DOI: https://doi.org/10.1039/b802311e
  • Primary Citation of Related Structures:  
    2QDS, 2QDT

  • PubMed Abstract: 

    The development of broad-spectrum metallo-beta-lactamase (MBL) inhibitors is challenging due to structural diversity and differences in metal utilisation by these enzymes. Analysis of structural data, followed by non-denturing mass spectrometric analyses, identified thiols proposed to inhibit representative MBLs from all three sub-classes: B1, B2 and B3. Solution analyses led to the identification of broad spectrum inhibitors, including potent inhibitors of the CphA MBL (Aeromonas hydrophila). Structural studies revealed that, as observed for other B1 and B3 MBLs, inhibition of the L1 MBL thiols involves metal chelation. Evidence is reported that this is not the case for inhibition of the CphA enzyme by some thiols; the crystal structure of the CphA-Zn-inhibitor complex reveals a binding mode in which the thiol does not interact with the zinc. The structural data enabled the design and the production of further more potent inhibitors. Overall the results suggest that the development of reasonably broad-spectrum MBL inhibitors should be possible.


  • Organizational Affiliation

    Chemistry Research Laboratory and OCISB, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.


Macromolecules
Find similar proteins by:  (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
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
MCO
Query on MCO

Download Ideal Coordinates CCD File 
G [auth A]1-(3-MERCAPTO-2-METHYL-PROPIONYL)-PYRROLIDINE-2-CARBOXYLIC ACID
C9 H15 N O3 S
FAKRSMQSSFJEIM-RNFRBKRXSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
E [auth A],
F [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
H [auth A],
I [auth A]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
MCO Binding MOAD:  2QDS Ki: 7.20e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.66 Å
  • R-Value Free: 0.170 
  • R-Value Work: 0.148 
  • R-Value Observed: 0.149 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 43.001α = 90
b = 100.99β = 90
c = 116.819γ = 90
Software Package:
Software NamePurpose
CCP4model building
REFMACrefinement
MAR345dtbdata collection
MOSFLMdata reduction
SCALAdata scaling
CCP4phasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-07-17
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description