View source for 6y2j


==Crystal structure of M. tuberculosis KasA in complex with 4,4,4-trifluoro-N-(isoquinolin-6-yl)butane-1-sulfonamide==
<StructureSection load='6y2j' size='340' side='right'caption='[[6y2j]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6y2j]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Y2J OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6Y2J FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=O6W:4,4,4-tris(fluoranyl)-~{N}-isoquinolin-6-yl-butane-1-sulfonamide'>O6W</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-ketoacyl-[acyl-carrier-protein]_synthase_I Beta-ketoacyl-[acyl-carrier-protein] synthase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.41 2.3.1.41] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6y2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y2j OCA], [http://pdbe.org/6y2j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6y2j RCSB], [http://www.ebi.ac.uk/pdbsum/6y2j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6y2j ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/FAB1_MYCTU FAB1_MYCTU]] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP (By similarity). 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In the course of optimizing a novel indazole sulfonamide series that inhibits beta-ketoacyl-ACP synthase (KasA) of Mycobacterium tuberculosis, a mutagenic aniline metabolite was identified. Further lead optimization efforts were therefore dedicated to eliminating this critical liability by removing the embedded aniline moiety or modifying its steric or electronic environment. While the narrow SAR space against the target ultimately rendered this goal unsuccessful, key structural knowledge around the binding site of this underexplored target for TB was generated to inform future discovery efforts.

Exploring the SAR of the beta-Ketoacyl-ACP Synthase Inhibitor GSK3011724A and Optimization around a Genotoxic Metabolite.,Cunningham F, Esquivias J, Fernandez-Menendez R, Perez A, Guardia A, Escribano J, Rivero C, Vimal M, Cacho M, de Dios-Anton P, Martinez-Martinez MS, Jimenez E, Huertas Valentin L, Rebollo-Lopez MJ, Lopez-Roman EM, Sousa-Morcuende V, Rullas J, Neu M, Chung CW, Bates RH ACS Infect Dis. 2020 Mar 20. doi: 10.1021/acsinfecdis.9b00493. PMID:32196311<ref>PMID:32196311</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6y2j" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Chung, C]]
[[Category: Acyltransferase]]
[[Category: Fatty acid biosynthesis]]
[[Category: Inhibitor]]
[[Category: Kasa]]
[[Category: Lipid synthesis]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Transferase]]