2vba

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[[Image:2vba.jpg|left|200px]]
 
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{{Structure
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==beta-ketoacyl-ACP synthase I (KAS) from E. coli with bound amino- thiazole inhibitor==
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|PDB= 2vba |SIZE=350|CAPTION= <scene name='initialview01'>2vba</scene>, resolution 1.36&Aring;
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<StructureSection load='2vba' size='340' side='right'caption='[[2vba]], [[Resolution|resolution]] 1.36&Aring;' scene=''>
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|SITE= <scene name='pdbsite=AC1:P4t+Binding+Site+For+Chain+A'>AC1</scene>
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=P4T:'>P4T</scene>
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<table><tr><td colspan='2'>[[2vba]] 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=2VBA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VBA FirstGlance]. <br>
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|ACTIVITY= [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]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.36&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P4T:2-PHENYLAMINO-4-METHYL-5-ACETYL+THIAZOLE'>P4T</scene></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vba OCA], [https://pdbe.org/2vba PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vba RCSB], [https://www.ebi.ac.uk/pdbsum/2vba PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vba ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vb/2vba_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2vba ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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'''BETA-KETOACYL-ACP SYNTHASE I (KAS) FROM E. COLI WITH BOUND AMINO-THIAZOLE INHIBITOR'''
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2vba" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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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.
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*[[Acyl carrier protein synthase 3D structures|Acyl carrier protein synthase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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2VBA is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VBA OCA].
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__TOC__
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</StructureSection>
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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/18084068 18084068]
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[[Category: Beta-ketoacyl-acyl-carrier-protein synthase I]]
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[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Bailly, J.]]
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[[Category: Bailly J]]
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[[Category: Hennig, M.]]
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[[Category: Hennig M]]
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[[Category: Pappenberger, G.]]
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[[Category: Pappenberger G]]
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[[Category: Schulz-Gasch, T.]]
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[[Category: Schulz-Gasch T]]
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[[Category: P4T]]
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[[Category: acyltransferase]]
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[[Category: amino-thiazole]]
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[[Category: antibiotic]]
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[[Category: cytoplasm]]
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[[Category: fatty acid biosynthesis]]
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[[Category: fatty acid synthesis]]
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[[Category: lipid synthesis]]
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[[Category: transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:45:08 2008''
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Current revision

beta-ketoacyl-ACP synthase I (KAS) from E. coli with bound amino- thiazole inhibitor

PDB ID 2vba

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