5FQ9

Crystal structure of the OXA10 with 1C


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.181 
  • R-Value Work: 0.157 
  • R-Value Observed: 0.158 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 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
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BETA-LACTAMASE OXA-10
A, B
248Pseudomonas aeruginosaMutation(s): 0 
EC: 3.5.2.6
UniProt
Find proteins for P14489 (Pseudomonas aeruginosa)
Explore P14489 
Go to UniProtKB:  P14489
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP14489
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
C6S
Query on C6S

Download Ideal Coordinates CCD File 
C [auth A],
I [auth B]
(3R)-3-(cyclohexylcarbonylamino)-2-oxidanyl-3,4-dihydro-1,2-benzoxaborinine-8-carboxylic acid
C16 H20 B N O5
ZRHUJXRVIMMHFG-ZDUSSCGKSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
F [auth A],
J [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ACT
Query on ACT

Download Ideal Coordinates CCD File 
G [auth A]ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
CL
Query on CL

Download Ideal Coordinates CCD File 
H [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
NA
Query on NA

Download Ideal Coordinates CCD File 
K [auth B]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
KCX
Query on KCX
A, B
L-PEPTIDE LINKINGC7 H14 N2 O4LYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.181 
  • R-Value Work: 0.157 
  • R-Value Observed: 0.158 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.898α = 90
b = 103.109β = 90
c = 125.529γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
MOSFLMdata reduction
SCALAdata scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


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 1.2: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description