View source for 2wgg


==Crystal Structure of Mycobacterium tuberculosis C171Q KasA variant with bound TLM==
<StructureSection load='2wgg' size='340' side='right'caption='[[2wgg]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2wgg]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WGG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WGG 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=TLM:THIOLACTOMYCIN'>TLM</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=2wgg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wgg OCA], [https://pdbe.org/2wgg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wgg RCSB], [https://www.ebi.ac.uk/pdbsum/2wgg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wgg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KASA_MYCTU KASA_MYCTU] Part of the mycobacterial fatty acid elongation system FAS-II, which is involved in mycolic acid biosynthesis. Catalyzes the elongation of long chain acyl-ACP substrates by the addition of two carbons from malonyl-ACP to an acyl acceptor (PubMed:11600501, PubMed:12023885, PubMed:12464486, PubMed:16873379, PubMed:22017312, PubMed:24108128). Involved in the initial extension of the mycolate chain and forms monounsaturated fatty acids that averaged 40 carbons in length (PubMed:12464486).<ref>PMID:11600501</ref> <ref>PMID:12023885</ref> <ref>PMID:12464486</ref> <ref>PMID:16873379</ref> <ref>PMID:22017312</ref> <ref>PMID:24108128</ref> 
== 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/wg/2wgg_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=2wgg ConSurf].
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== Publication Abstract from PubMed ==
Mycobacteria have a unique cell wall consisting of mycolic acids, very-long-chain lipids that provide protection and allow the bacteria to persist within human macrophages. Inhibition of cell wall biosynthesis is fatal for the organism and a starting point for the discovery and development of novel antibiotics. We determined the crystal structures of KasA, a key enzyme involved in the biosynthesis of long-chain fatty acids, in its apo-form and bound to the natural product inhibitor thiolactomycin. Detailed insights into the interaction of the inhibitor with KasA and the identification of a polyethylene glycol molecule that mimics a fatty acid substrate of approximately 40 carbon atoms length, represent the first atomic view of a mycobacterial enzyme involved in the synthesis of long-chain fatty acids and provide a robust platform for the development of novel thiolactomycin analogs with high affinity for KasA.

Crystal structures of Mycobacterium tuberculosis KasA show mode of action within cell wall biosynthesis and its inhibition by thiolactomycin.,Luckner SR, Machutta CA, Tonge PJ, Kisker C Structure. 2009 Jul 15;17(7):1004-13. PMID:19604480<ref>PMID:19604480</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Acyl carrier protein synthase 3D structures|Acyl carrier protein synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Kisker C]]
[[Category: Luckner SR]]