RCSB PDB - 6FJ1: Structure of the Ldtfm-avibactam carbamoyl enzyme

 6FJ1

Structure of the Ldtfm-avibactam carbamoyl enzyme


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.69 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.199 

Starting Model: experimental
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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted NXLClick on this verticalbar to view detailsBest fitted P3GClick on this verticalbar to view details

This is version 1.3 of the entry. See complete history


Literature

Synthesis of Avibactam Derivatives and Activity on beta-Lactamases and Peptidoglycan Biosynthesis Enzymes of Mycobacteria.

Edoo, Z.Iannazzo, L.Compain, F.Li de la Sierra Gallay, I.van Tilbeurgh, H.Fonvielle, M.Bouchet, F.Le Run, E.Mainardi, J.L.Arthur, M.Etheve-Quelquejeu, M.Hugonnet, J.E.

(2018) Chemistry 24: 8081-8086

  • DOI: https://doi.org/10.1002/chem.201800923
  • Primary Citation of Related Structures:  
    6FJ1

  • PubMed Abstract: 

    There is a renewed interest for β-lactams for treating infections due to Mycobacterium tuberculosis and M. abscessus because their β-lactamases are inhibited by classical (clavulanate) or new generation (avibactam) inhibitors, respectively. Here, access to an azido derivative of the diazabicyclooctane (DBO) scaffold of avibactam for functionalization by the Huisgen-Sharpless cycloaddition reaction is reported. The amoxicillin-DBO combinations were active, indicating that the triazole ring is compatible with drug penetration (minimal inhibitory concentration of 16 μg mL -1 for both species). Mechanistically, β-lactamase inhibition was not sufficient to account for the potentiation of amoxicillin by DBOs. Thus, the latter compounds were investigated as inhibitors of l,d-transpeptidases (Ldts), which are the main peptidoglycan polymerases in mycobacteria. The DBOs acted as slow-binding inhibitors of Ldts by S-carbamoylation indicating that optimization of DBOs for Ldt inhibition is an attractive strategy to obtain drugs selectively active on mycobacteria.


  • Organizational Affiliation

    Sorbonne Université, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, INSERM, Centre de Recherche des Cordeliers, CRC, 75006, Paris, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
L,D-TRANSPEPTIDASE
A, B, C
258Enterococcus faeciumMutation(s): 0 
Gene Names: CQR42_01530
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NXL
Query on NXL

Download Ideal Coordinates CCD File 
E [auth A],
I [auth B],
O [auth C]
(2S,5R)-1-formyl-5-[(sulfooxy)amino]piperidine-2-carboxamide
C7 H13 N3 O6 S
WJDGWXPPFHLLNL-RITPCOANSA-N
P3G
Query on P3G

Download Ideal Coordinates CCD File 
D [auth A],
J [auth B],
P [auth C]
3,6,9,12,15-PENTAOXAHEPTADECANE
C12 H26 O5
HYDWALOBQJFOMS-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
F [auth A]
G [auth A]
K [auth B]
L [auth B]
M [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
H [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.69 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.199 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 208.54α = 90
b = 131.97β = 90.14
c = 70.09γ = 90
Software Package:
Software NamePurpose
XDSdata reduction
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted NXLClick on this verticalbar to view detailsBest fitted P3GClick on this verticalbar to view details

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Fondation pour la recherche medicaleFranceECO20160736080
French National Research AgencyFranceANR-17-CE18-0010-03

Revision History  (Full details and data files)

  • Version 1.0: 2019-01-30
    Type: Initial release
  • Version 1.1: 2023-06-21
    Changes: Database references, Structure summary
  • Version 1.2: 2024-02-07
    Changes: Data collection, Refinement description
  • Version 1.3: 2024-10-23
    Changes: Structure summary