View source for 4j3f


==Crystal Structure of FabI from F. tularensis in complex with novel inhibitors based on the benzimidazole scaffold.==
<StructureSection load='4j3f' size='340' side='right'caption='[[4j3f]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4j3f]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Francisella_tularensis_subsp._tularensis_SCHU_S4 Francisella tularensis subsp. tularensis SCHU S4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J3F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J3F 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]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1JT:1-(4-METHOXY-3-METHYLBENZYL)-5,6,7,8-TETRAHYDRO-1H-NAPHTHO[2,3-D]IMIDAZOLE'>1JT</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <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=4j3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j3f OCA], [https://pdbe.org/4j3f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j3f RCSB], [https://www.ebi.ac.uk/pdbsum/4j3f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j3f ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q5NGQ3_FRATT Q5NGQ3_FRATT] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Francisella tularensis, the causative agent of tularemia, presents a significant biological threat and is a Category A priority pathogen due to its potential for weaponization. The bacterial FASII pathway is a viable target for the development of novel antibacterial agents treating Gram-negative infections. Here we report the advancement of a promising series of benzimidazole FabI (enoyl-ACP reductase) inhibitors to a second-generation using a systematic, structure-guided lead optimization strategy, and the determination of several co-crystal structures that confirm the binding mode of designed inhibitors. These compounds display an improved low nanomolar enzymatic activity as well as promising low microgram/mL antibacterial activity against both F. tularensis and Staphylococcus aureus and its methicillin-resistant strain (MRSA). The improvements in activity accompanying structural modifications lead to a better understanding of the relationship between the chemical structure and biological activity that encompasses both enzymatic and whole-cell activity.

Structural and biological evaluation of a novel series of benzimidazole inhibitors of Francisella tularensis enoyl-ACP reductase (FabI).,Mehboob S, Song J, Hevener KE, Su PC, Boci T, Brubaker L, Truong L, Mistry T, Deng J, Cook JL, Santarsiero BD, Ghosh AK, Johnson ME Bioorg Med Chem Lett. 2015 Mar 15;25(6):1292-6. doi: 10.1016/j.bmcl.2015.01.048. , Epub 2015 Jan 29. PMID:25677657<ref>PMID:25677657</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4j3f" 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 subsp. tularensis SCHU S4]]
[[Category: Large Structures]]
[[Category: Boci T]]
[[Category: Brubaker L]]
[[Category: Johnson ME]]
[[Category: Mehboob S]]
[[Category: Santarsiero BD]]