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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.== | | ==Structure of MurA (UDP-N-acetylglucosamine enolpyruvyl transferase), from Vibrio fischeri in complex with substrate UDP-N-acetylglucosamine and the drug fosfomycin.== |
| - | <StructureSection load='3vcy' size='340' side='right' caption='[[3vcy]], [[Resolution|resolution]] 1.93Å' scene=''> | + | <StructureSection load='3vcy' size='340' side='right'caption='[[3vcy]], [[Resolution|resolution]] 1.93Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3vcy]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Aiivibrio_fischeri_mj11 Aiivibrio fischeri mj11]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VCY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VCY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3vcy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aliivibrio_fischeri_MJ11 Aliivibrio fischeri MJ11]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VCY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VCY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FFQ:[(1R)-1-HYDROXYPROPYL]PHOSPHONIC+ACID'>FFQ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.925Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">murA, VFMJ11_0391 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=388396 Aiivibrio fischeri MJ11])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FFQ:[(1R)-1-HYDROXYPROPYL]PHOSPHONIC+ACID'>FFQ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-N-acetylglucosamine_1-carboxyvinyltransferase UDP-N-acetylglucosamine 1-carboxyvinyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.7 2.5.1.7] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3vcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vcy OCA], [https://pdbe.org/3vcy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vcy RCSB], [https://www.ebi.ac.uk/pdbsum/3vcy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vcy ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vcy OCA], [http://pdbe.org/3vcy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vcy RCSB], [http://www.ebi.ac.uk/pdbsum/3vcy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vcy ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MURA_VIBFM MURA_VIBFM]] Cell wall formation. Adds enolpyruvyl to UDP-N-acetylglucosamine (By similarity). | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Enoylpyruvate transferase|Enoylpyruvate transferase]] | + | *[[Enoylpyruvate transferase 3D structures|Enoylpyruvate transferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aiivibrio fischeri mj11]] | + | [[Category: Aliivibrio fischeri MJ11]] |
| - | [[Category: UDP-N-acetylglucosamine 1-carboxyvinyltransferase]] | + | [[Category: Large Structures]] |
| - | [[Category: Bensen, D C]] | + | [[Category: Bensen DC]] |
| - | [[Category: Cunningham, M L]] | + | [[Category: Cunningham ML]] |
| - | [[Category: Nix, J]] | + | [[Category: Nix J]] |
| - | [[Category: Rodriguez, S]] | + | [[Category: Rodriguez S]] |
| - | [[Category: Tari, L W]] | + | [[Category: Tari LW]] |
| - | [[Category: Amino sugar and nucleotide sugar metabolism]]
| + | |
| - | [[Category: Cytosol]]
| + | |
| - | [[Category: Fosfomycin]]
| + | |
| - | [[Category: Mura]]
| + | |
| - | [[Category: Peptidoglycan]]
| + | |
| - | [[Category: Peptidoglycan biosynthesis]]
| + | |
| - | [[Category: Transferase-antibiotic complex]]
| + | |
| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bensen DC, Rodriguez S, Nix J, Cunningham ML, Tari LW. 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 Struct Biol Cryst Commun. 2012 Apr 1;68(Pt 4):382-5. Epub, 2012 Mar 27. PMID:22505403 doi:10.1107/S1744309112006720
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