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| - | [[Image:1fj4.jpg|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1fj4| PDB=1fj4 | SCENE= }} | | {{STRUCTURE_1fj4| PDB=1fj4 | SCENE= }} |
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| - | '''THE STRUCTURE OF BETA-KETOACYL-[ACYL CARRIER PROTEIN] SYNTHASE I IN COMPLEX WITH THIOLACTOMYCIN, IMPLICATIONS FOR DRUG DESIGN'''
| + | ===THE STRUCTURE OF BETA-KETOACYL-[ACYL CARRIER PROTEIN] SYNTHASE I IN COMPLEX WITH THIOLACTOMYCIN, IMPLICATIONS FOR DRUG DESIGN=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_11050088}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 11050088 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_11050088}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Fatty acid elongation]] | | [[Category: Fatty acid elongation]] |
| | [[Category: Thiolactomycin]] | | [[Category: Thiolactomycin]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 16:23:20 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 03:20:53 2008'' |
Revision as of 00:20, 1 July 2008
Template:STRUCTURE 1fj4
THE STRUCTURE OF BETA-KETOACYL-[ACYL CARRIER PROTEIN] SYNTHASE I IN COMPLEX WITH THIOLACTOMYCIN, IMPLICATIONS FOR DRUG DESIGN
Template:ABSTRACT PUBMED 11050088
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
Page seeded by OCA on Tue Jul 1 03:20:53 2008
