1W2X

Crystal structure of the carboxyltransferase domain of acetyl- coenzyme A carboxylase in complex with CP-640186

Summary for 1W2X

• Entry DOI: 10.2210/pdb1w2x/pdb
• Related: 1OD2 1OD4 1UYR 1UYS 1UYT 1UYV
• Descriptor: ACETYL-COA CARBOXYLASE, (3R)-1'-(9-ANTHRYLCARBONYL)-3-(MORPHOLIN-4-YLCARBONYL)-1,4'-BIPIPERIDINE (3 entities in total)
• Functional Keywords: transferase, acetyl-coa carboxylase, carboxyltransferase, cp-640186, inhibitor, acc, ct
• Biological source: SACCHAROMYCES CEREVISIAE
• Cellular location: Cytoplasm: Q00955
• Total number of polymer chains: 3
• Total formula weight: 259089.23

Authors

Zhang, H.,Tweel, B.,Li, J.,Tong, L. (deposition date: 2004-07-09, release date: 2004-09-09, Last modification date: 2024-05-08)

Primary citation

Zhang, H.,Tweel, B.,Li, J.,Tong, L.
Crystal Structure of the Carboxyltransferase Domain of Acetyl-Coenzyme a Carboxylase in Complex with Cp-640186
Structure, 12:1683-, 2004

PubMed Abstract: 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.

PubMed: 15341732
DOI: 10.1016/J.STR.2004.07.009

Experimental method

X-RAY DIFFRACTION (2.8 Å)