3vcy

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

spinqualitylabelsall models 3vcy, resolution 1.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3vcy is a 4 chain structure with sequence from Aliivibrio fischeri MJ11. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.925Å Ligands: FFQ, GOL, PO4, UD1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MURA_ALIFM Cell wall formation. Adds enolpyruvyl to UDP-N-acetylglucosamine.[HAMAP-Rule:MF_00111] Publication Abstract from PubMed 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 A. 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. Structure of MurA (UDP-N-acetylglucosamine enolpyruvyl transferase) from Vibrio fischeri in complex with substrate UDP-N-acetylglucosamine and the drug fosfomycin.,Bensen DC, Rodriguez S, Nix J, Cunningham ML, Tari LW Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Apr 1;68(Pt 4):382-5. Epub, 2012 Mar 27. PMID:22505403 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Enoylpyruvate transferase 3D structures

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