6p9k
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Mycobacterium tuberculosis KasA in complex with O6G== | |
| + | <StructureSection load='6p9k' size='340' side='right'caption='[[6p9k]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6p9k]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P9K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6P9K FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=O6G:N-(2-cyano-3-methyl-1H-indol-5-yl)butane-1-sulfonamide'>O6G</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5w2o|5w2o]], [[5w2p|5w2p]], [[5w2q|5w2q]], [[5w2s|5w2s]]</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6p9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p9k OCA], [http://pdbe.org/6p9k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p9k RCSB], [http://www.ebi.ac.uk/pdbsum/6p9k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p9k ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Published Mycobacterium tuberculosis beta-ketoacyl-ACP synthase KasA inhibitors lack sufficient potency and/or pharmacokinetic properties. A structure-based approach was used to optimize existing KasA inhibitor DG167. This afforded indazole JSF-3285 with a 30-fold increase in mouse plasma exposure. Biochemical, genetic, and X-ray studies confirmed JSF-3285 targets KasA. JSF-3285 offers substantial activity in an acute mouse model of infection and in the corresponding chronic infection model, with efficacious reductions in colony-forming units at doses as low as 5 mg/kg once daily orally and improvement of the efficacy of front-line drugs isoniazid or rifampicin. JSF-3285 is a promising preclinical candidate for tuberculosis. | ||
| - | + | A Preclinical Candidate Targeting Mycobacterium tuberculosis KasA.,Inoyama D, Awasthi D, Capodagli GC, Tsotetsi K, Sukheja P, Zimmerman M, Li SG, Jadhav R, Russo R, Wang X, Grady C, Richmann T, Shrestha R, Li L, Ahn YM, Ho Liang HP, Mina M, Park S, Perlin DS, Connell N, Dartois V, Alland D, Neiditch MB, Kumar P, Freundlich JS Cell Chem Biol. 2020 Mar 19. pii: S2451-9456(20)30071-4. doi:, 10.1016/j.chembiol.2020.02.007. PMID:32197094<ref>PMID:32197094</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Neiditch, M | + | <div class="pdbe-citations 6p9k" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Capodagli, G C]] | ||
| + | [[Category: Neiditch, M B]] | ||
| + | [[Category: Beta ketoacyl synthase i]] | ||
| + | [[Category: Fatty acid biosynthesis]] | ||
| + | [[Category: Lipid synthesis]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 09:15, 1 April 2020
Crystal structure of Mycobacterium tuberculosis KasA in complex with O6G
| |||||||||||
