1w2x: Difference between revisions

Revision as of 16:39, 21 February 2008

CRYSTAL STRUCTURE OF THE CARBOXYLTRANSFERASE DOMAIN OF ACETYL-COENZYME A CARBOXYLASE IN COMPLEX WITH CP-640186

OverviewOverview

Acetyl-coenzyme A carboxylases (ACCs) are important targets for the development of therapeutic agents against obesity, diabetes, and other diseases. CP-640186 is a potent inhibitor of mammalian ACCs and can reduce body weight and improve insulin sensitivity in test animals. It is believed to target the carboxyltransferase (CT) domain of these enzymes. Here we report the crystal structure of the yeast CT domain in complex with CP-640186. The inhibitor is bound in the active site at the interface of a dimer of the CT domain. CP-640186 has tight interactions with the putative biotin binding site in the CT domain and demonstrates a distinct mode of inhibiting the CT activity as compared to the herbicides that inhibit plant ACCs. The affinity of inhibitors for the CT domain has been assessed using kinetic and fluorescence anisotropy binding studies. The structural information identifies three regions for drug binding in the active site of CT.

About this StructureAbout this Structure

1W2X is a Single protein structure of sequence from Saccharomyces cerevisiae with as ligand. Active as Acetyl-CoA carboxylase, with EC number 6.4.1.2 Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in complex with CP-640186., Zhang H, Tweel B, Li J, Tong L, Structure. 2004 Sep;12(9):1683-91. PMID:15341732

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 ==Overview==
-Acetyl-coenzyme A carboxylases (ACCs) are important targets for the, development of therapeutic agents against obesity, diabetes, and other, diseases. CP-640186 is a potent inhibitor of mammalian ACCs and can reduce, body weight and improve insulin sensitivity in test animals. It is, believed to target the carboxyltransferase (CT) domain of these enzymes., Here we report the crystal structure of the yeast CT domain in complex, with CP-640186. The inhibitor is bound in the active site at the interface, of a dimer of the CT domain. CP-640186 has tight interactions with the, putative biotin binding site in the CT domain and demonstrates a distinct, mode of inhibiting the CT activity as compared to the herbicides that, inhibit plant ACCs. The affinity of inhibitors for the CT domain has been, assessed using kinetic and fluorescence anisotropy binding studies. The, structural information identifies three regions for drug binding in the, active site of CT.
+Acetyl-coenzyme A carboxylases (ACCs) are important targets for the development of therapeutic agents against obesity, diabetes, and other diseases. CP-640186 is a potent inhibitor of mammalian ACCs and can reduce body weight and improve insulin sensitivity in test animals. It is believed to target the carboxyltransferase (CT) domain of these enzymes. Here we report the crystal structure of the yeast CT domain in complex with CP-640186. The inhibitor is bound in the active site at the interface of a dimer of the CT domain. CP-640186 has tight interactions with the putative biotin binding site in the CT domain and demonstrates a distinct mode of inhibiting the CT activity as compared to the herbicides that inhibit plant ACCs. The affinity of inhibitors for the CT domain has been assessed using kinetic and fluorescence anisotropy binding studies. The structural information identifies three regions for drug binding in the active site of CT.
 ==About this Structure==
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 [[Category: inhibitor]]
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