5FQA

Crystal Structure of Bacillus cereus Metallo-Beta-Lactamase II


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.10 Å
  • R-Value Free: 0.140 
  • R-Value Work: 0.119 
  • R-Value Observed: 0.120 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Use of ferrous iron by metallo-beta-lactamases.

Cahill, S.T.Tarhonskaya, H.Rydzik, A.M.Flashman, E.McDonough, M.A.Schofield, C.J.Brem, J.

(2016) J Inorg Biochem 163: 185-193

  • DOI: https://doi.org/10.1016/j.jinorgbio.2016.07.013
  • Primary Citation of Related Structures:  
    5FQA

  • PubMed Abstract: 

    Metallo-β-lactamases (MBLs) catalyse the hydrolysis of almost all β-lactam antibacterials including the latest generation carbapenems and are a growing worldwide clinical problem. It is proposed that MBLs employ one or two zinc ion cofactors in vivo. Isolated MBLs are reported to use transition metal ions other than zinc, including copper, cadmium and manganese, with iron ions being a notable exception. We report kinetic and biophysical studies with the di-iron(II)-substituted metallo-β-lactamase II from Bacillus cereus (di-Fe(II) BcII) and the clinically relevant B1 subclass Verona integron-encoded metallo-β-lactamase 2 (di-Fe(II) VIM-2). The results reveal that MBLs can employ ferrous iron in catalysis, but with altered kinetic and inhibition profiles compared to the zinc enzymes. A crystal structure of di-Fe(II) BcII reveals only small overall changes in the active site compared to the di-Zn(II) enzyme including retention of the di-metal bridging water; however, the positions of the metal ions are altered in the di-Fe(II) compared to the di-Zn(II) structure. Stopped-flow analyses reveal that the mechanism of nitrocefin hydrolysis by both di-Fe(II) BcII and di-Fe(II) VIM-2 is altered compared to the di-Zn(II) enzymes. Notably, given that the MBLs are the subject of current medicinal chemistry efforts, the results raise the possibility the Fe(II)-substituted MBLs may be of clinical relevance under conditions of low zinc availability, and reveal potential variation in inhibitor activity against the differently metallated MBLs.


  • Organizational Affiliation

    Chemistry Research Laboratory, Oxford, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BETA-LACTAMASE 2227Bacillus cereusMutation(s): 0 
EC: 3.5.2.6
UniProt
Find proteins for P04190 (Bacillus cereus)
Explore P04190 
Go to UniProtKB:  P04190
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04190
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SO4
Query on SO4

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

Download Ideal Coordinates CCD File 
D [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
EDO
Query on EDO

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G [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
FE
Query on FE

Download Ideal Coordinates CCD File 
B [auth A],
C [auth A]
FE (III) ION
Fe
VTLYFUHAOXGGBS-UHFFFAOYSA-N
OH
Query on OH

Download Ideal Coordinates CCD File 
F [auth A]HYDROXIDE ION
H O
XLYOFNOQVPJJNP-UHFFFAOYSA-M
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CSD
Query on CSD
A
L-PEPTIDE LINKINGC3 H7 N O4 SCYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.10 Å
  • R-Value Free: 0.140 
  • R-Value Work: 0.119 
  • R-Value Observed: 0.120 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.048α = 90
b = 61.5β = 92.98
c = 69.469γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
MOSFLMdata reduction
Aimlessdata scaling
PHENIXphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-08-10
    Type: Initial release
  • Version 1.1: 2016-08-24
    Changes: Database references
  • Version 1.2: 2016-09-21
    Changes: Database references, Other
  • Version 1.3: 2016-11-16
    Changes: Database references
  • Version 1.4: 2018-03-28
    Changes: Database references
  • Version 1.5: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description