4c6v: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4c6v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C6V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C6V FirstGlance]. <br> | <table><tr><td colspan='2'>[[4c6v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C6V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C6V FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TLG:(5R)-3-ACETYL-4-HYDROXY-5-METHYL-5-[(1Z)-2-METHYLBUTA-1,3-DIEN-1-YL]THIOPHEN-2(5H)-ONE'>TLG</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TLG:(5R)-3-ACETYL-4-HYDROXY-5-METHYL-5-[(1Z)-2-METHYLBUTA-1,3-DIEN-1-YL]THIOPHEN-2(5H)-ONE'>TLG</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=4c6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c6v OCA], [https://pdbe.org/4c6v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c6v RCSB], [https://www.ebi.ac.uk/pdbsum/4c6v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c6v ProSAT]</span></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=4c6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c6v OCA], [https://pdbe.org/4c6v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c6v RCSB], [https://www.ebi.ac.uk/pdbsum/4c6v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c6v ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The 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<ref>PMID:24108128</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4c6v" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Acyl carrier protein synthase 3D structures|Acyl carrier protein synthase 3D structures]] | *[[Acyl carrier protein synthase 3D structures|Acyl carrier protein synthase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 15:05, 20 December 2023
Crystal structure of M. tuberculosis KasA in complex with TLM5 (Soak for 5 min)Crystal structure of M. tuberculosis KasA in complex with TLM5 (Soak for 5 min)
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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