6p9k: Difference between revisions

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-'''Unreleased structure'''
-The entry 6p9k is ON HOLD
+==Crystal structure of Mycobacterium tuberculosis KasA in complex with O6G==
+<StructureSection load='6p9k' size='340' side='right'caption='[[6p9k]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6p9k]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. 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 [https://proteopedia.org/fgij/fg.htm?mol=6P9K 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]] 1.703&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6p9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p9k OCA], [https://pdbe.org/6p9k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p9k RCSB], [https://www.ebi.ac.uk/pdbsum/6p9k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p9k ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/KASA_MYCTU KASA_MYCTU] Part of the mycobacterial fatty acid elongation system FAS-II, which is involved in mycolic acid biosynthesis. Catalyzes the elongation of long chain acyl-ACP substrates by the addition of two carbons from malonyl-ACP to an acyl acceptor (PubMed:11600501, PubMed:12023885, PubMed:12464486, PubMed:16873379, PubMed:22017312, PubMed:24108128). Involved in the initial extension of the mycolate chain and forms monounsaturated fatty acids that averaged 40 carbons in length (PubMed:12464486).<ref>PMID:11600501</ref> <ref>PMID:12023885</ref> <ref>PMID:12464486</ref> <ref>PMID:16873379</ref> <ref>PMID:22017312</ref> <ref>PMID:24108128</ref>
+<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.
-Authors: Capodagli, G.C., Neiditch, M.B.
+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>
-Description: Crystal structure of Mycobacterium tuberculosis KasA in complex with JF5
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Capodagli, G.C]]
+<div class="pdbe-citations 6p9k" style="background-color:#fffaf0;"></div>
-[[Category: Neiditch, M.B]]
+==See Also==
+*[[Acyl carrier protein synthase 3D structures|Acyl carrier protein synthase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mycobacterium tuberculosis]]
+[[Category: Capodagli GC]]
+[[Category: Neiditch MB]]