3uic
From Proteopedia
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| - | [[ | + | ==Crystal Structure of FabI, an Enoyl Reductase from F. tularensis, in complex with a Novel and Potent Inhibitor== |
| + | <StructureSection load='3uic' size='340' side='right' caption='[[3uic]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3uic]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Francisella_tularensis_subsp._tularensis Francisella tularensis subsp. tularensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UIC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UIC FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=09T:1-(3,4-DICHLOROBENZYL)-5,6-DIMETHYL-1H-BENZIMIDAZOLE'>09T</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fabI, fabI Coordinates 801554-802336, FTT_0782 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=119856 Francisella tularensis subsp. tularensis])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3uic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uic OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3uic RCSB], [http://www.ebi.ac.uk/pdbsum/3uic PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Because of structural and mechanistic differences between eukaryotic and prokaryotic fatty acid synthesis enzymes, the bacterial pathway, FAS-II, is an attractive target for the design of antimicrobial agents. We have previously reported the identification of a novel series of benzimidazole compounds with particularly good antibacterial effect against Francisella tularensis, a Category A biowarfare pathogen. Herein we report the crystal structure of the F. tularensis FabI enzyme in complex with our most active benzimidazole compound bound with NADH. The structure reveals that the benzimidazole compounds bind to the substrate site in a unique conformation that is distinct from the binding motif of other known FabI inhibitors. Detailed inhibition kinetics have confirmed that the compounds possess a novel inhibitory mechanism that is unique among known FabI inhibitors. These studies could have a strong impact on future antimicrobial design efforts and may reveal new avenues for the design of FAS-II active antibacterial compounds. | ||
| - | + | Structural and enzymatic analyses reveal the binding mode of a novel series of Francisella tularensis enoyl reductase (FabI) inhibitors.,Mehboob S, Hevener KE, Truong K, Boci T, Santarsiero BD, Johnson ME J Med Chem. 2012 Jun 28;55(12):5933-41. Epub 2012 Jun 8. PMID:22642319<ref>PMID:22642319</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Enoyl-Acyl-Carrier Protein Reductase|Enoyl-Acyl-Carrier Protein Reductase]] | *[[Enoyl-Acyl-Carrier Protein Reductase|Enoyl-Acyl-Carrier Protein Reductase]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Francisella tularensis subsp. tularensis]] | [[Category: Francisella tularensis subsp. tularensis]] | ||
| - | [[Category: Johnson, M E | + | [[Category: Johnson, M E]] |
| - | [[Category: Mehboob, S | + | [[Category: Mehboob, S]] |
| - | [[Category: Santarsiero, B D | + | [[Category: Santarsiero, B D]] |
| - | [[Category: Truong, K | + | [[Category: Truong, K]] |
[[Category: Enoyl reductase]] | [[Category: Enoyl reductase]] | ||
[[Category: Nadh binding]] | [[Category: Nadh binding]] | ||
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | ||
[[Category: Rossmann fold]] | [[Category: Rossmann fold]] | ||
Revision as of 15:00, 9 December 2014
Crystal Structure of FabI, an Enoyl Reductase from F. tularensis, in complex with a Novel and Potent Inhibitor
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