View source for 2jjy


==Crystal structure of Francisella tularensis enoyl reductase (ftFabI) with bound NAD==
<StructureSection load='2jjy' size='340' side='right'caption='[[2jjy]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2jjy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Francisella_tularensis Francisella tularensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JJY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JJY 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]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=2jjy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jjy OCA], [https://pdbe.org/2jjy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jjy RCSB], [https://www.ebi.ac.uk/pdbsum/2jjy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jjy ProSAT]</span></td></tr>
</table>
== 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/jj/2jjy_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=2jjy ConSurf].
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== Publication Abstract from PubMed ==
Francisella tularensis is a highly virulent and contagious gram-negative intracellular bacterium that causes the disease tularemia in mammals. The high infectivity and the ability of the bacterium to survive for weeks in a cool, moist environment have raised the possibility that this organism could be exploited deliberately as a potential biological weapon. Fatty acid biosynthesis (FAS-II) is essential for bacterial viability and has been validated as a target for the discovery of novel antibacterials. The FAS-II enoyl reductase ftuFabI has been cloned and expressed, and a series of diphenyl ethers have been identified that are subnanomolar inhibitors of the enzyme with MIC90 values as low as 0.00018 mug/ml. The existence of a linear correlation between the Ki and MIC values strongly suggests that the antibacterial activity of the diphenyl ethers results from direct inhibition of ftuFabI within the cell. The compounds are slow onset inhibitors of ftuFabI, and the residence time of the inhibitors on the enzyme correlates with their in vivo activity in a mouse model of tularemia infection. Significantly, the rate of breakdown of the enzyme-inhibitor complex is a better predictor of in vivo activity than the overall thermodynamic stability of the complex, a concept that has important implications for the discovery of novel chemotherapeutics that normally rely on equilibrium measurements of potency.

Slow-Onset Inhibition of the FabI Enoyl Reductase from Francisella Tularensis: Residence Time and In Vivo Activity.,Lu H, England K, Am Ende C, Truglio J, Luckner S, Bommineni G, Marlenee N, Knudson S, Knudson D, Bowen R, Kisker C, Slayden R, Tonge P ACS Chem Biol. 2009 Feb 10. PMID:19206187<ref>PMID:19206187</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 2jjy" style="background-color:#fffaf0;"></div>

==See Also==
*[[Enoyl-Acyl-Carrier Protein Reductase 3D structures|Enoyl-Acyl-Carrier Protein Reductase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Francisella tularensis]]
[[Category: Large Structures]]
[[Category: Kisker C]]
[[Category: Lu H]]
[[Category: Luckner SR]]
[[Category: Tonge PJ]]
[[Category: Truglio JJ]]