2vba
From Proteopedia
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|PDB= 2vba |SIZE=350|CAPTION= <scene name='initialview01'>2vba</scene>, resolution 1.36Å | |PDB= 2vba |SIZE=350|CAPTION= <scene name='initialview01'>2vba</scene>, resolution 1.36Å | ||
|SITE= <scene name='pdbsite=AC1:P4t+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:P4t+Binding+Site+For+Chain+A'>AC1</scene> | ||
| - | |LIGAND= <scene name='pdbligand=P4T:'>P4T</scene> | + | |LIGAND= <scene name='pdbligand=P4T:2-PHENYLAMINO-4-METHYL-5-ACETYL+THIAZOLE'>P4T</scene> |
| - | |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] | + | |ACTIVITY= <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> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1f91|1F91]], [[1fj8|1FJ8]], [[1g5x|1G5X]], [[1h4f|1H4F]], [[2aq7|2AQ7]], [[2aqb|2AQB]], [[2buh|2BUH]], [[2bui|2BUI]], [[2byx|2BYX]], [[2bz3|2BZ3]], [[1dd8|1DD8]], [[1ek4|1EK4]], [[1fj4|1FJ4]], [[2byw|2BYW]], [[2byy|2BYY]], [[2byz|2BYZ]], [[2bz4|2BZ4]], [[2vb7|2VB7]], [[2vb8|2VB8]], [[2vb9|2VB9]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vba OCA], [http://www.ebi.ac.uk/pdbsum/2vba PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2vba RCSB]</span> | ||
}} | }} | ||
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[[Category: Pappenberger, G.]] | [[Category: Pappenberger, G.]] | ||
[[Category: Schulz-Gasch, T.]] | [[Category: Schulz-Gasch, T.]] | ||
| - | [[Category: P4T]] | ||
[[Category: acyltransferase]] | [[Category: acyltransferase]] | ||
[[Category: amino-thiazole]] | [[Category: amino-thiazole]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:10:39 2008'' |
Revision as of 02:10, 31 March 2008
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| , resolution 1.36Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | |||||||
| Activity: | Beta-ketoacyl-acyl-carrier-protein synthase I, with EC number 2.3.1.41 | ||||||
| Related: | 1F91, 1FJ8, 1G5X, 1H4F, 2AQ7, 2AQB, 2BUH, 2BUI, 2BYX, 2BZ3, 1DD8, 1EK4, 1FJ4, 2BYW, 2BYY, 2BYZ, 2BZ4, 2VB7, 2VB8, 2VB9
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
BETA-KETOACYL-ACP SYNTHASE I (KAS) FROM E. COLI WITH BOUND AMINO-THIAZOLE INHIBITOR
Overview
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.
About this Structure
2VBA is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
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
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