5FQC

Crystal structure of the metallo-beta-lactamase VIM-2 with 2C

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.45 Å
  • R-Value Free: 0.184 
  • R-Value Work: 0.155 
  • R-Value Observed: 0.155 

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This is version 2.1 of the entry. See complete history. 


Literature

Structural basis of metallo-beta-lactamase, serine-beta-lactamase and penicillin-binding protein inhibition by cyclic boronates.

Brem, J., Cain, R., Cahill, S., McDonough, M.A., Clifton, I.J., Jimenez-Castellanos, J.C., Avison, M.B., Spencer, J., Fishwick, C.W., Schofield, C.J.

(2016) Nat Commun 7: 12406-12406

  • DOI: https://doi.org/10.1038/ncomms12406
  • Primary Citation of Related Structures:  
    5FQ9, 5FQB, 5FQC, 5J8X

  • PubMed Abstract: 

    β-Lactamases enable resistance to almost all β-lactam antibiotics. Pioneering work revealed that acyclic boronic acids can act as 'transition state analogue' inhibitors of nucleophilic serine enzymes, including serine-β-lactamases. Here we report biochemical and biophysical analyses revealing that cyclic boronates potently inhibit both nucleophilic serine and zinc-dependent β-lactamases by a mechanism involving mimicking of the common tetrahedral intermediate. Cyclic boronates also potently inhibit the non-essential penicillin-binding protein PBP 5 by the same mechanism of action. The results open the way for development of dual action inhibitors effective against both serine- and metallo-β-lactamases, and which could also have antimicrobial activity through inhibition of PBPs.

    • Organizational Affiliation: 

    Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK.


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BETA-LACTAMASE
A, B
242Pseudomonas aeruginosaMutation(s): 0 
EC: 3.5.2.6
UniProt
Find proteins for Q9K2N0 (Pseudomonas aeruginosa)
Explore Q9K2N0 
Go to UniProtKB:  Q9K2N0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9K2N0
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
OK3
Query on OK3
Download Ideal Coordinates CCD File 
H [auth A],
O [auth B]		(4~{R})-4-[[4-(aminomethyl)phenyl]carbonylamino]-3,3-bis(oxidanyl)-2-oxa-3-boranuidabicyclo[4.4.0]deca-1(10),6,8-triene-10-carboxylic acid
C17 H18 B N2 O6
QLXKUYDHLJOWQG-AWEZNQCLSA-N
DMS
Query on DMS
Download Ideal Coordinates CCD File 
I [auth A]DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
ZN
Query on ZN
Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
G [auth A]
L [auth B]
M [auth B]
E [auth A],
F [auth A],
G [auth A],
L [auth B],
M [auth B],
N [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
FMT
Query on FMT
Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
J [auth B],
K [auth B]		FORMIC ACID
C H2 O2
BDAGIHXWWSANSR-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
OK3 Binding MOAD:  5FQC IC50: 3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.45 Å
  • R-Value Free: 0.184 
  • R-Value Work: 0.155 
  • R-Value Observed: 0.155 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 101.931α = 90
b = 79.152β = 130.16
c = 67.135γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
SCALEPACKdata scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-08-17
    Type: Initial release
  • Version 1.1: 2018-02-21
    Changes: Database references
  • Version 2.0: 2019-10-30
    Changes: Data collection, Derived calculations, Experimental preparation, Non-polymer description, Other, Structure summary
  • Version 2.1: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Refinement description