2FHX

Pseudomonas aeruginosa SPM-1 metallo-beta-lactamase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.194 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Crystal Structure of Pseudomonas aeruginosa SPM-1 Provides Insights into Variable Zinc Affinity of Metallo-beta-lactamases.

Murphy, T.A.Catto, L.E.Halford, S.E.Hadfield, A.T.Minor, W.Walsh, T.R.Spencer, J.

(2006) J Mol Biol 357: 890-903

  • DOI: https://doi.org/10.1016/j.jmb.2006.01.003
  • Primary Citation of Related Structures:  
    2FHX

  • PubMed Abstract: 

    Metallo-beta-lactamases (mbetals) confer broad-spectrum resistance to beta-lactam antibiotics upon host bacteria and escape the action of existing beta-lactamase inhibitors. SPM-1 is a recently discovered mbetal that is distinguished from related enzymes by possession of a substantial central insertion and by sequence variation at positions that maintain active site structure. Biochemical data show SPM-1 to contain two Zn2+ sites of differing affinities, a phenomenon that is well documented amongst mbetals but for which a structural explanation has proved elusive. Here, we report the crystal structure of SPM-1 to 1.9 A resolution. The structure reveals SPM-1 to lack a mobile loop implicated in substrate binding by related mbetals and to accommodate the central insertion in an extended helical interdomain region. Deleting this had marginal effect upon binding and hydrolysis of a range of beta-lactams. These data suggest that the interactions of SPM-1 with substrates differ from those employed by other mbetals. SPM-1 as crystallised contains a single Zn2+. Both the active site hydrogen-bonding network and main-chain geometry at Asp120, a key component of the binding site for the second zinc ion, differ significantly from previous mbetal structures. We propose that variable interactions made by the Asp120 carbonyl group modulate affinity for a second Zn2+ equivalent in mbetals of the B1 subfamily. We further predict that SPM-1 possesses the capacity to evolve variants of enhanced catalytic activity by point mutations altering geometry and hydrogen bonding in the vicinity of the second Zn2+ site.


  • Organizational Affiliation

    Department of Cellular and Molecular Medicine, University of Bristol School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SPM-1246Pseudomonas aeruginosaMutation(s): 1 
Gene Names: blaSPM-1
EC: 3.5.2.6
UniProt
Find proteins for Q8G9Q0 (Pseudomonas aeruginosa)
Explore Q8G9Q0 
Go to UniProtKB:  Q8G9Q0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8G9Q0
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
SPM-1246Pseudomonas aeruginosaMutation(s): 1 
Gene Names: blaSPM-1
EC: 3.5.2.6
UniProt
Find proteins for Q8G9Q0 (Pseudomonas aeruginosa)
Explore Q8G9Q0 
Go to UniProtKB:  Q8G9Q0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8G9Q0
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZN
Query on ZN

Download Ideal Coordinates CCD File 
C [auth A],
H [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
AZI
Query on AZI

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
I [auth B]
AZIDE ION
N3
IVRMZWNICZWHMI-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
J [auth B]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Modified Residues  2 Unique
IDChains TypeFormula2D DiagramParent
CSD
Query on CSD
A
L-PEPTIDE LINKINGC3 H7 N O4 SCYS
CSO
Query on CSO
B
L-PEPTIDE LINKINGC3 H7 N O3 SCYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.194 
  • Space Group: H 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 126.936α = 90
b = 126.936β = 90
c = 90.461γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
SOLVEphasing
RESOLVEphasing
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-01-17
    Type: Initial release
  • Version 1.1: 2008-04-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2014-11-12
    Changes: Non-polymer description
  • Version 1.4: 2017-10-18
    Changes: Refinement description
  • Version 1.5: 2022-04-13
    Changes: Database references, Derived calculations, Structure summary