Crystal structure of the 500-kDa yeast ACC, a 13-year quest for a 'Holy Grail'

Acetyl-CoA carboxylase (ACC) has crucial roles in fatty acid metabolism and is an attractive target for drug discovery against diabetes, cancer and other diseases. ACC contains biotin carboxylase (BC) and carboxyltransferase (CT) activities, and its biotin is linked covalently to the biotin carboxyl carrier protein (BCCP). Most eukaryotic ACCs are 250-kDa, multi-domain enzymes and function as homo-dimers and higher oligomers. We have determined the crystal structure of the full-length, 500-kDa holoenzyme dimer of yeast ACC. The structure is strikingly different from those of the other biotin-dependent carboxylases. It defines how the two active sites are organized in the holoenzyme, and reveals a novel molecular mechanism for the regulation of this enzyme. The determination of this structure represents the culmination of 13 years of effort on this target. [J. Wei & L. Tong. (2015). Crystal structure of the 500-kDa yeast acetyl-CoA carboxylase holoenzyme dimer. Nature, 526, 723-727.]

Business Office

Department of Biological Sciences
500 Fairchild Center
Mail Code 2401
Columbia University
1212 Amsterdam Avenue
New York, NY 10027

Academic Office

Department of Biological Sciences
600 Fairchild Center
Mail Code 2402
Columbia University
1212 Amsterdam Avenue
New York, NY 10027
biology@columbia.edu
212 854-4581