4c71: Difference between revisions
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==Crystal structure of M. tuberculosis C171Q KasA in complex with TLM18== | ==Crystal structure of M. tuberculosis C171Q KasA in complex with TLM18== | ||
<StructureSection load='4c71' size='340' side='right' caption='[[4c71]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='4c71' size='340' side='right' caption='[[4c71]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4c71]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4c71]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C71 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C71 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7RD:(R,E)-3-(4-AZIDOBUTYL)-4-HYDROXY-5-METHYL-5-(2-METHYLBUTA-1,3-DIEN-1-YL)THIOPHEN-2(5H)-ONE'>7RD</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=M7U:(2R)-2-(HEXADECANOYLOXY)-3-{[(10R)-10-METHYLOCTADECANOYL]OXY}PROPYL+PHOSPHATE'>M7U</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7RD:(R,E)-3-(4-AZIDOBUTYL)-4-HYDROXY-5-METHYL-5-(2-METHYLBUTA-1,3-DIEN-1-YL)THIOPHEN-2(5H)-ONE'>7RD</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=M7U:(2R)-2-(HEXADECANOYLOXY)-3-{[(10R)-10-METHYLOCTADECANOYL]OXY}PROPYL+PHOSPHATE'>M7U</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c6u|4c6u]], [[4c6v|4c6v]], [[4c6w|4c6w]], [[4c6x|4c6x]], [[4c6z|4c6z]], [[4c70|4c70]], [[4c72|4c72]], [[4c73|4c73]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c6u|4c6u]], [[4c6v|4c6v]], [[4c6w|4c6w]], [[4c6x|4c6x]], [[4c6z|4c6z]], [[4c70|4c70]], [[4c72|4c72]], [[4c73|4c73]]</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='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=4c71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c71 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4c71 RCSB], [http://www.ebi.ac.uk/pdbsum/4c71 PDBsum]</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=4c71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c71 OCA], [http://pdbe.org/4c71 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4c71 RCSB], [http://www.ebi.ac.uk/pdbsum/4c71 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4c71 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4c71" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Acyl carrier protein synthase|Acyl carrier protein synthase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Myctu]] | ||
[[Category: Bommineni, G R]] | [[Category: Bommineni, G R]] | ||
[[Category: Fekete, A]] | [[Category: Fekete, A]] | ||
Revision as of 19:47, 11 August 2016
Crystal structure of M. tuberculosis C171Q KasA in complex with TLM18Crystal structure of M. tuberculosis C171Q KasA in complex with TLM18
Structural highlights
Publication Abstract from PubMedThe survival of Mycobacterium tuberculosis depends on mycolic acids - very long alpha-alkyl-beta-hydroxy fatty acids comprising 60 to 90 carbon atoms. However, despite considerable efforts, little is known about how enzymes involved in mycolic acid biosynthesis recognize and bind their hydrophobic fatty acyl substrates. The condensing enzyme KasA is pivotal for the synthesis of very long (C38-42) fatty acids, the precursors of mycolic acids. To probe the mechanism of substrate and inhibitor recognition by KasA, we determined the structure of this protein in complex with a mycobacterial phospholipid, and with several thiolactomycin derivatives that were designed as substrate analogs. Our structures provide consecutive snapshots along the reaction coordinate for the enzyme-catalyzed reaction, and support an induced-fit mechanism in which a wide cavity is established through the concerted opening of three gatekeeping residues and several alpha-helices. The stepwise characterization of the binding process provides mechanistic insights into the induced-fit recognition in this system and serves as an excellent foundation for the development of high affinity KasA inhibitors. Structural Basis for the Recognition of Mycolic Acid Precursors by KasA, a Condensing Enzyme and Drug Target from Mycobacterium Tuberculosis.,Schiebel J, Kapilashrami K, Fekete A, Bommineni GR, Schaefer CM, Mueller MJ, Tonge PJ, Kisker C J Biol Chem. 2013 Oct 9. PMID:24108128[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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