2vb8: Difference between revisions

Revision as of 18:32, 4 May 2008

BETA-KETOACYL-ACP SYNTHASE I (KAS) FROM E. COLI WITH BOUND INHIBITOR THIOLACTOMYCIN

OverviewOverview

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 StructureAbout this Structure

2VB8 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sun May 4 18:32:19 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:2vb8.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2vb8 |SIZE=350|CAPTION= <scene name='initialview01'>2vb8</scene>, resolution 1.52&Aring;
+The line below this paragraph, containing "STRUCTURE_2vb8", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:Tlm+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Tlm+Binding+Site+For+Chain+B'>AC2</scene>, <scene name='pdbsite=AC3:Tlm+Binding+Site+For+Chain+C'>AC3</scene>, <scene name='pdbsite=AC4:Tlm+Binding+Site+For+Chain+D'>AC4</scene>, <scene name='pdbsite=AC5:Cl+Binding+Site+For+Chain+A'>AC5</scene> and <scene name='pdbsite=AC6:Cl+Binding+Site+For+Chain+B'>AC6</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=TLM:THIOLACTOMYCIN'>TLM</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|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>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_2vb8|  PDB=2vb8  |  SCENE=  }}
-|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]], [[2vb9|2VB9]], [[2vba|2VBA]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vb8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vb8 OCA], [http://www.ebi.ac.uk/pdbsum/2vb8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2vb8 RCSB]</span>
-}}
 '''BETA-KETOACYL-ACP SYNTHASE I (KAS) FROM E. COLI WITH BOUND INHIBITOR THIOLACTOMYCIN'''
@@ Line 30: / Line 27: @@
 [[Category: Pappenberger, G.]]
 [[Category: Schulz-Gasch, T.]]
-[[Category: acyltransferase]]
+[[Category: Acyltransferase]]
-[[Category: antibiotic]]
+[[Category: Antibiotic]]
-[[Category: cytoplasm]]
+[[Category: Cytoplasm]]
-[[Category: fatty acid biosynthesis]]
+[[Category: Fatty acid biosynthesis]]
-[[Category: fatty acid synthesis]]
+[[Category: Fatty acid synthesis]]
-[[Category: lipid synthesis]]
+[[Category: Lipid synthesis]]
-[[Category: thiolactomycin]]
+[[Category: Thiolactomycin]]
-[[Category: transferase]]
+[[Category: Transferase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 18:32:19 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:10:40 2008''