3vcy
From Proteopedia
(Difference between revisions)
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/MURA_ALIFM MURA_ALIFM] Cell wall formation. Adds enolpyruvyl to UDP-N-acetylglucosamine.[HAMAP-Rule:MF_00111] | [https://www.uniprot.org/uniprot/MURA_ALIFM MURA_ALIFM] Cell wall formation. Adds enolpyruvyl to UDP-N-acetylglucosamine.[HAMAP-Rule:MF_00111] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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. | ||
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| + | 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<ref>PMID:22505403</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 3vcy" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Enoylpyruvate transferase 3D structures|Enoylpyruvate transferase 3D structures]] | *[[Enoylpyruvate transferase 3D structures|Enoylpyruvate transferase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Structure of MurA (UDP-N-acetylglucosamine enolpyruvyl transferase), from Vibrio fischeri in complex with substrate UDP-N-acetylglucosamine and the drug fosfomycin.
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