View source for 2uup


==Crystal structure of MurD ligase in complex with D-Glu containing sulfonamide inhibitor==
<StructureSection load='2uup' size='340' side='right'caption='[[2uup]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2uup]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UUP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UUP 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]] 1.88&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=LK4:N-({6-[(4-CYANOBENZYL)OXY]NAPHTHALEN-2-YL}SULFONYL)-D-GLUTAMIC+ACID'>LK4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2uup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uup OCA], [https://pdbe.org/2uup PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2uup RCSB], [https://www.ebi.ac.uk/pdbsum/2uup PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2uup ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MURD_ECOLI MURD_ECOLI] Cell wall formation. Catalyzes the addition of glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanine (UMA).[HAMAP-Rule:MF_00639]
== 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/uu/2uup_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=2uup ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mur ligases have essential roles in the biosynthesis of peptidoglycan, and they represent attractive targets for the design of novel antibacterials. MurD (UDP- N-acetylmuramoyl- l-alanine: d-glutamate ligase) is the second enzyme in the series of Mur ligases, and it catalyzes the addition of d-glutamic acid ( d-Glu) to the cytoplasmic intermediate UDP- N-acetylmuramoyl- l-alanine (UMA). Because of the high binding affinity of d-Glu toward MurD, we synthesized and biochemically evaluated a series of N-substituted d-Glu derivatives as potential inhibitors of MurD from E. coli, which allowed us to explore the structure-activity relationships. The substituted naphthalene- N-sulfonyl- d-Glu inhibitors, which were synthesized as potential transition-state analogues, displayed IC 50 values ranging from 80 to 600 muM. In addition, the high-resolution crystal structures of MurD in complex with four novel inhibitors revealed details of the binding mode of the inhibitors within the active site of MurD. Structure-activity relationships and cocrystal structures constitute an excellent starting point for further development of novel MurD inhibitors of this structural class.

Novel Naphthalene-N-sulfonyl-d-glutamic Acid Derivatives as Inhibitors of MurD, a Key Peptidoglycan Biosynthesis Enzyme.,Humljan J, Kotnik M, Contreras-Martel C, Blanot D, Urleb U, Dessen A, Solmajer T, Gobec S J Med Chem. 2008 Nov 13. PMID:19007109<ref>PMID:19007109</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 2uup" style="background-color:#fffaf0;"></div>

==See Also==
*[[Mur ligase|Mur ligase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Blanot D]]
[[Category: Contreras-Martel C]]
[[Category: Dessen A]]
[[Category: Gobec S]]
[[Category: Humljan J]]
[[Category: Kotnik M]]
[[Category: Solmajer T]]
[[Category: Urleb U]]