1fj4
From Proteopedia
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| - | [[Image:1fj4.jpg|left|200px]] | + | [[Image:1fj4.jpg|left|200px]] |
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| - | '''THE STRUCTURE OF BETA-KETOACYL-[ACYL CARRIER PROTEIN] SYNTHASE I IN COMPLEX WITH THIOLACTOMYCIN, IMPLICATIONS FOR DRUG DESIGN''' | + | {{Structure |
| + | |PDB= 1fj4 |SIZE=350|CAPTION= <scene name='initialview01'>1fj4</scene>, resolution 2.35Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=TLM:THIOLACTOMYCIN'>TLM</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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''THE STRUCTURE OF BETA-KETOACYL-[ACYL CARRIER PROTEIN] SYNTHASE I IN COMPLEX WITH THIOLACTOMYCIN, IMPLICATIONS FOR DRUG DESIGN''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1FJ4 is a [ | + | 1FJ4 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=1FJ4 OCA]. |
==Reference== | ==Reference== | ||
| - | Inhibition of beta-ketoacyl-acyl carrier protein synthases by thiolactomycin and cerulenin. Structure and mechanism., Price AC, Choi KH, Heath RJ, Li Z, White SW, Rock CO, J Biol Chem. 2001 Mar 2;276(9):6551-9. Epub 2000 Oct 24. PMID:[http:// | + | Inhibition of beta-ketoacyl-acyl carrier protein synthases by thiolactomycin and cerulenin. Structure and mechanism., Price AC, Choi KH, Heath RJ, Li Z, White SW, Rock CO, J Biol Chem. 2001 Mar 2;276(9):6551-9. Epub 2000 Oct 24. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11050088 11050088] |
[[Category: Beta-ketoacyl-acyl-carrier-protein synthase I]] | [[Category: Beta-ketoacyl-acyl-carrier-protein synthase I]] | ||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
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[[Category: White, S W.]] | [[Category: White, S W.]] | ||
[[Category: TLM]] | [[Category: TLM]] | ||
| - | [[Category: condensing | + | [[Category: condensing enzyme]] |
[[Category: drug design]] | [[Category: drug design]] | ||
[[Category: fatty acid elongation]] | [[Category: fatty acid elongation]] | ||
[[Category: thiolactomycin]] | [[Category: thiolactomycin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:09:54 2008'' |
Revision as of 09:09, 20 March 2008
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| , resolution 2.35Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Beta-ketoacyl-acyl-carrier-protein synthase I, with EC number 2.3.1.41 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
THE STRUCTURE OF BETA-KETOACYL-[ACYL CARRIER PROTEIN] SYNTHASE I IN COMPLEX WITH THIOLACTOMYCIN, IMPLICATIONS FOR DRUG DESIGN
Overview
The beta-ketoacyl-acyl carrier protein (ACP) synthases are key regulators of type II fatty acid synthesis and are the targets for two natural products, thiolactomycin (TLM) and cerulenin. The high resolution structures of the FabB-TLM and FabB-cerulenin binary complexes were determined. TLM mimics malonyl-ACP in the FabB active site. It forms strong hydrogen bond interactions with the two catalytic histidines, and the unsaturated alkyl side chain interaction with a small hydrophobic pocket is stabilized by pi stacking interactions. Cerulenin binding mimics the condensation transition state. The subtle differences between the FabB-cerulenin and FabF-cerulenin (Moche, M., Schneider, G., Edwards, P., Dehesh, K., and Lindqvist, Y. (1999) J. Biol. Chem. 244, 6031-6034) structures explain the differences in the sensitivity of the two enzymes to the antibiotic and may reflect the distinct substrate specificities that differentiate the two enzymes. The FabB[H333N] protein was prepared to convert the FabB His-His-Cys active site triad into the FabH His-Asn-Cys configuration to test the importance of the two His residues in TLM and cerulenin binding. FabB[H333N] was significantly more resistant to both antibiotics than FabB and had an affinity for TLM an order of magnitude less than the wild-type enzyme, illustrating that the two-histidine active site architecture is critical to protein-antibiotic interaction. These data provide a structural framework for understanding antibiotic sensitivity within this group of enzymes.
About this Structure
1FJ4 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Inhibition of beta-ketoacyl-acyl carrier protein synthases by thiolactomycin and cerulenin. Structure and mechanism., Price AC, Choi KH, Heath RJ, Li Z, White SW, Rock CO, J Biol Chem. 2001 Mar 2;276(9):6551-9. Epub 2000 Oct 24. PMID:11050088
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