View source for 2aq7


==Structure-activity relationships at the 5-posiiton of thiolactomycin: an intact 5(R)-isoprene unit is required for activity against the condensing enzymes from Mycobacterium tuberculosis and Escherichia coli==
<StructureSection load='2aq7' size='340' side='right'caption='[[2aq7]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2aq7]] is a 4 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=2AQ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AQ7 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TL5:(5R)-4-HYDROXY-3,5-DIMETHYL-5-[(1E,3E)-2-METHYLPENTA-1,3-DIENYL]THIOPHEN-2(5H)-ONE'>TL5</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=2aq7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aq7 OCA], [https://pdbe.org/2aq7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aq7 RCSB], [https://www.ebi.ac.uk/pdbsum/2aq7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aq7 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FABB_ECOLI FABB_ECOLI] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Specific for elongation from C-10 to unsaturated C-16 and C-18 fatty acids.
== 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/aq/2aq7_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=2aq7 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Thiolactomycin inhibits bacterial cell growth through inhibition of the beta-ketoacyl-ACP synthase activity of type II fatty acid synthases. The effect of modifications of the 5-position isoprenoid side chain on both IC(50) and MIC were determined. Synthesis and screening of a structurally diverse set of 5-position analogues revealed very little tolerance for substitution in purified enzyme assays, but a few analogues retained MIC, presumably through another target. Even subtle modifications such as reducing one or both double bonds of the diene were not tolerated. The only permissible structural modifications were removal of the isoprene methyl group or addition of a methyl group to the terminus. Cocrystallization of these two inhibitors with the condensing enzyme from Escherichia coli revealed that they retained the TLM binding mode at the active site with reduced affinity. These results suggest a strict requirement for a conjugated, planar side chain inserting within the condensing enzyme active site.

Structure-activity relationships at the 5-position of thiolactomycin: an intact (5R)-isoprene unit is required for activity against the condensing enzymes from Mycobacterium tuberculosis and Escherichia coli.,Kim P, Zhang YM, Shenoy G, Nguyen QA, Boshoff HI, Manjunatha UH, Goodwin MB, Lonsdale J, Price AC, Miller DJ, Duncan K, White SW, Rock CO, Barry CE 3rd, Dowd CS J Med Chem. 2006 Jan 12;49(1):159-71. PMID:16392800<ref>PMID:16392800</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2aq7" style="background-color:#fffaf0;"></div>

==See Also==
*[[Acyl carrier protein synthase 3D structures|Acyl carrier protein synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Boshoff HI]]
[[Category: Goodwin MB]]
[[Category: Kim P]]
[[Category: Lonsdale J]]
[[Category: Manjunatha UH]]
[[Category: Miller DJ]]
[[Category: Nguyen QA]]
[[Category: Price AC]]
[[Category: Shenoy G]]
[[Category: Zhang YM]]