3VCY

Structure of MurA (UDP-N-acetylglucosamine enolpyruvyl transferase), from Vibrio fischeri in complex with substrate UDP-N-acetylglucosamine and the drug fosfomycin.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.93 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.202 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structure of MurA (UDP-N-acetylglucosamine enolpyruvyl transferase) from Vibrio fischeri in complex with substrate UDP-N-acetylglucosamine and the drug fosfomycin.

Bensen, D.C.Rodriguez, S.Nix, J.Cunningham, M.L.Tari, L.W.

(2012) Acta Crystallogr Sect F Struct Biol Cryst Commun 68: 382-385

  • DOI: https://doi.org/10.1107/S1744309112006720
  • Primary Citation of Related Structures:  
    3VCY

  • PubMed Abstract: 

    The development of new antibiotics is necessitated by the rapid development of resistance to current therapies. UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), which catalyzes the first committed step of bacterial peptidoglycan biosynthesis, is a prime candidate for therapeutic intervention. MurA is the target of the antibiotic fosfomycin, a natural product produced by Streptomyces. Despite possessing a high degree of sequence conservation with MurA enzymes from fosfomycin-susceptible organisms, recent microbiological studies suggest that MurA from Vibrio fischeri (VfiMurA) may confer fosfomycin resistance via a mechanism that is not yet understood. The crystal structure of VfiMurA in a ternary complex with the substrate UDP-N-acetylglucosamine (UNAG) and fosfomycin has been solved to a resolution of 1.93 Å. Fosfomycin is known to inhibit MurA by covalently binding to a highly conserved cysteine in the active site of the enzyme. A comparison of the title structure with the structure of fosfomycin-susceptible Haemophilus influenzae MurA (PDB entry 2rl2) revealed strikingly similar conformations of the mobile substrate-binding loop and clear electron density for a fosfomycin-cysteine adduct. Based on these results, there are no distinguishing sequence/structural features in VfiMurA that would translate to a diminished sensitivity to fosfomycin. However, VfiMurA is a robust crystallizer and shares high sequence identity with many clinically relevant bacterial pathogens. Thus, it would serve as an ideal system for use in the structure-guided optimization of new antibacterial agents.


  • Organizational Affiliation

    Structural Biology, Trius Therapeutics, 6310 Nancy Ridge Drive, Suite 101, San Diego, CA 92008, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
UDP-N-acetylglucosamine 1-carboxyvinyltransferase
A, B, C, D
430Aliivibrio fischeri MJ11Mutation(s): 0 
Gene Names: murAVFMJ11_0391
EC: 2.5.1.7
UniProt
Find proteins for B5F9P4 (Aliivibrio fischeri (strain MJ11))
Explore B5F9P4 
Go to UniProtKB:  B5F9P4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupB5F9P4
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
UD1
Query on UD1

Download Ideal Coordinates CCD File 
F [auth A],
I [auth B],
M [auth C],
Q [auth D]
URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE
C17 H27 N3 O17 P2
LFTYTUAZOPRMMI-CFRASDGPSA-N
FFQ
Query on FFQ

Download Ideal Coordinates CCD File 
E [auth A],
J [auth B],
O [auth C],
T [auth D]
[(1R)-1-hydroxypropyl]phosphonic acid
C3 H9 O4 P
MVIJUJBSAAUHEM-GSVOUGTGSA-N
PO4
Query on PO4

Download Ideal Coordinates CCD File 
G [auth A],
K [auth B],
N [auth C],
R [auth D]
PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
GOL
Query on GOL

Download Ideal Coordinates CCD File 
H [auth A],
L [auth B],
P [auth C],
S [auth D]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.93 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.202 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.6α = 90
b = 118.51β = 116.48
c = 92.51γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
PHASERphasing
REFMACrefinement
CrystalCleardata reduction
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-04-11
    Type: Initial release
  • Version 1.1: 2012-04-25
    Changes: Database references
  • Version 1.2: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description