3VCY

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

Summary for 3VCY

• Entry DOI: 10.2210/pdb3vcy/pdb
• Descriptor: UDP-N-acetylglucosamine 1-carboxyvinyltransferase, [(1R)-1-hydroxypropyl]phosphonic acid, URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE, ... (6 entities in total)
• Functional Keywords: mura, fosfomycin, peptidoglycan, amino sugar and nucleotide sugar metabolism, peptidoglycan biosynthesis, cytosol, transferase-antibiotic complex, transferase/antibiotic
• Biological source: Vibrio fischeri
• Cellular location: Cytoplasm (By similarity): B5F9P4
• Total number of polymer chains: 4
• Total formula weight: 186938.77

Authors

Bensen, D.C.,Rodriguez, S.,Nix, J.,Cunningham, M.L.,Tari, L.W. (deposition date: 2012-01-04, release date: 2012-04-11, Last modification date: 2024-10-30)

Primary citation

Bensen, D.C.,Rodriguez, S.,Nix, J.,Cunningham, M.L.,Tari, L.W.
Structure of MurA (UDP-N-acetylglucosamine enolpyruvyl transferase) from Vibrio fischeri in complex with substrate UDP-N-acetylglucosamine and the drug fosfomycin.
Acta Crystallogr.,Sect.F, 68:382-385, 2012

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.

PubMed: 22505403
DOI: 10.1107/S1744309112006720

Experimental method

X-RAY DIFFRACTION (1.925 Å)