View source for 1ybg


==MurA inhibited by a derivative of 5-sulfonoxy-anthranilic acid==
<StructureSection load='1ybg' size='340' side='right'caption='[[1ybg]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ybg]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterobacter_cloacae Enterobacter cloacae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YBG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YBG FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IAS:BETA-L-ASPARTIC+ACID'>IAS</scene>, <scene name='pdbligand=TAV:N-METHYL-N-{2-[(2-NAPHTHYLSULFONYL)AMINO]-5-[(2-NAPHTHYLSULFONYL)OXY]BENZOYL}-L-ASPARTIC+ACID'>TAV</scene></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=1ybg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ybg OCA], [https://pdbe.org/1ybg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ybg RCSB], [https://www.ebi.ac.uk/pdbsum/1ybg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ybg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MURA_ENTCC MURA_ENTCC] Cell wall formation. Adds enolpyruvyl to UDP-N-acetylglucosamine. Target for the antibiotic phosphomycin.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yb/1ybg_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ybg ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
MurA (UDP-N-acetylglucosamine enolpyruvyl transferase, EC 2.5.1.7) catalyzes the first committed step in the synthesis of the bacterial cell wall. It is the target of the naturally occurring, broad-spectrum antibiotic fosfomycin. Fosfomycin, an epoxide, is a relatively poor drug because an ever-increasing number of bacteria have developed resistance to fosfomycin. Thus, there is a critical need for the development of novel drugs that target MurA by a different molecular mode of action. We have identified a new scaffold of potent MurA inhibitors, derivatives of 5-sulfonoxy-anthranilic acid, using high-throughput screening. T6361 and T6362 are competitive inhibitors of MurA with respect to the first substrate, UDP-N-acetylglucosamine (UNAG), with a K(i) of 16 microM. The crystal structure of the MurA.T6361 complex at 2.6 angstrom resolution, together with fluorescence data, revealed that the inhibitor targets a loop, Pro112 to Pro121, that is crucial for the structural changes of the enzyme during catalysis. Thus, this new class of MurA inhibitors is not active site-directed but instead obstructs the transition from the open (unliganded) to the closed (UNAG-liganded) enzyme form. The results provide evidence for the existence of a MurA.UNAG collision complex that may be specifically targeted by small molecules different from ground-state analogs of the enzymatic reaction.

A novel inhibitor that suspends the induced fit mechanism of UDP-N-acetylglucosamine enolpyruvyl transferase (MurA).,Eschenburg S, Priestman MA, Abdul-Latif FA, Delachaume C, Fassy F, Schonbrunn E J Biol Chem. 2005 Apr 8;280(14):14070-5. Epub 2005 Feb 8. PMID:15701635<ref>PMID:15701635</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1ybg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Enoylpyruvate transferase 3D structures|Enoylpyruvate transferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Enterobacter cloacae]]
[[Category: Large Structures]]
[[Category: Abdul-Latif FA]]
[[Category: Delachaume C]]
[[Category: Eschenburg S]]
[[Category: Fassy F]]
[[Category: Priestman MA]]
[[Category: Schonbrunn E]]