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==beta-ketoacyl-ACP synthase I (KAS) from E. coli, apo structure after soak in PEG solution== | |||
<StructureSection load='2vb7' size='340' side='right'caption='[[2vb7]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2vb7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VB7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VB7 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]] 1.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</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=2vb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vb7 OCA], [https://pdbe.org/2vb7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vb7 RCSB], [https://www.ebi.ac.uk/pdbsum/2vb7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vb7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/FABB_ECOLI FABB_ECOLI] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Specific for elongation from C-10 to unsaturated C-16 and C-18 fatty acids. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vb/2vb7_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vb7 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Fatty-acid synthesis in bacteria is of great interest as a target for the discovery of antibacterial compounds. The addition of a new acetyl moiety to the growing fatty-acid chain, an essential step in this process, is catalyzed by beta-ketoacyl-ACP synthase (KAS). It is inhibited by natural antibiotics such as cerulenin and thiolactomycin; however, these lack the requirements for optimal drug development. Structure-based biophysical screening revealed a novel synthetic small molecule, 2-phenylamino-4-methyl-5-acetylthiazole, that binds to Escherichia coli KAS I with a binding constant of 25 microM as determined by fluorescence titration. A 1.35 A crystal structure of its complex with its target reveals noncovalent interactions with the active-site Cys163 and hydrophobic residues of the fatty-acid binding pocket. The active site is accessible through an open conformation of the Phe392 side chain and no conformational changes are induced at the active site upon ligand binding. This represents a novel binding mode that differs from thiolactomycin or cerulenin interaction. The structural information on the protein-ligand interaction offers strategies for further optimization of this low-molecular-weight compound. | |||
Structure-assisted discovery of an aminothiazole derivative as a lead molecule for inhibition of bacterial fatty-acid synthesis.,Pappenberger G, Schulz-Gasch T, Kusznir E, Muller F, Hennig M Acta Crystallogr D Biol Crystallogr. 2007 Dec;63(Pt 12):1208-16. Epub 2007, Nov 16. PMID:18084068<ref>PMID:18084068</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2vb7" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Acyl carrier protein synthase 3D structures|Acyl carrier protein synthase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Bailly | [[Category: Bailly J]] | ||
[[Category: Hennig | [[Category: Hennig M]] | ||
[[Category: Pappenberger | [[Category: Pappenberger G]] | ||
[[Category: Schulz-Gasch | [[Category: Schulz-Gasch T]] | ||
Latest revision as of 04:26, 21 November 2024
beta-ketoacyl-ACP synthase I (KAS) from E. coli, apo structure after soak in PEG solutionbeta-ketoacyl-ACP synthase I (KAS) from E. coli, apo structure after soak in PEG solution
Structural highlights
FunctionFABB_ECOLI Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Specific for elongation from C-10 to unsaturated C-16 and C-18 fatty acids. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedFatty-acid synthesis in bacteria is of great interest as a target for the discovery of antibacterial compounds. The addition of a new acetyl moiety to the growing fatty-acid chain, an essential step in this process, is catalyzed by beta-ketoacyl-ACP synthase (KAS). It is inhibited by natural antibiotics such as cerulenin and thiolactomycin; however, these lack the requirements for optimal drug development. Structure-based biophysical screening revealed a novel synthetic small molecule, 2-phenylamino-4-methyl-5-acetylthiazole, that binds to Escherichia coli KAS I with a binding constant of 25 microM as determined by fluorescence titration. A 1.35 A crystal structure of its complex with its target reveals noncovalent interactions with the active-site Cys163 and hydrophobic residues of the fatty-acid binding pocket. The active site is accessible through an open conformation of the Phe392 side chain and no conformational changes are induced at the active site upon ligand binding. This represents a novel binding mode that differs from thiolactomycin or cerulenin interaction. The structural information on the protein-ligand interaction offers strategies for further optimization of this low-molecular-weight compound. Structure-assisted discovery of an aminothiazole derivative as a lead molecule for inhibition of bacterial fatty-acid synthesis.,Pappenberger G, Schulz-Gasch T, Kusznir E, Muller F, Hennig M Acta Crystallogr D Biol Crystallogr. 2007 Dec;63(Pt 12):1208-16. Epub 2007, Nov 16. PMID:18084068[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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