View source for 1xxe


==RDC refined solution structure of the AaLpxC/TU-514 complex==
<StructureSection load='1xxe' size='340' side='right'caption='[[1xxe]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1xxe]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1nzt 1nzt]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XXE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XXE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TUX:1,5-ANHYDRO-2-C-(CARBOXYMETHYL-N-HYDROXYAMIDE)-2-DEOXY-3-O-MYRISTOYL-D-GLUCITOL'>TUX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=1xxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xxe OCA], [https://pdbe.org/1xxe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xxe RCSB], [https://www.ebi.ac.uk/pdbsum/1xxe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xxe ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LPXC_AQUAE LPXC_AQUAE] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell (By similarity).
== 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/xx/1xxe_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=1xxe ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lipopolysaccharide, the major constituent of the outer monolayer of the outer membrane of Gram-negative bacteria, is anchored into the membrane through the hydrophobic moiety lipid A, a hexaacylated disaccharide. The zinc-dependent metalloamidase UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) catalyzes the second and committed step in the biosynthesis of lipid A. LpxC shows no homology to mammalian metalloamidases and is essential for cell viability, making it an important target for the development of novel antibacterial compounds. Recent NMR and X-ray studies of the LpxC from Aquifex aeolicus have provided the first structural information about this family of proteins. Insight into the catalytic mechanism and the design of effective inhibitors could be facilitated by more detailed structural and biochemical studies that define substrate-protein interactions and the roles of specific residues in the active site. Here, we report the synthesis of the (13)C-labeled substrate-analogue inhibitor TU-514, and the subsequent refinement of the solution structure of the A. aeolicus LpxC-TU-514 complex using residual dipolar couplings. We also reevaluate the catalytic role of an active site histidine, H253, on the basis of both its pK(a) as determined by NMR titration and pH-dependent kinetic analyses. These results provide a structural basis for the design of more potent LpxC inhibitors than those that are currently available.

Refined solution structure of the LpxC-TU-514 complex and pKa analysis of an active site histidine: insights into the mechanism and inhibitor design.,Coggins BE, McClerren AL, Jiang L, Li X, Rudolph J, Hindsgaul O, Raetz CR, Zhou P Biochemistry. 2005 Feb 1;44(4):1114-26. PMID:15667205<ref>PMID:15667205</ref>

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

==See Also==
*[[UDP-3-O-acyl-N-acetylglucosamine deacetylase|UDP-3-O-acyl-N-acetylglucosamine deacetylase]]
*[[UDP-3-O-acyl-N-acetylglucosamine deacetylase 3D structures|UDP-3-O-acyl-N-acetylglucosamine deacetylase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aquifex aeolicus]]
[[Category: Large Structures]]
[[Category: Coggins BE]]
[[Category: Hindsgaul O]]
[[Category: Jiang L]]
[[Category: Li X]]
[[Category: McClerren AL]]
[[Category: Raetz CRH]]
[[Category: Rudolph J]]
[[Category: Zhou P]]