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528590 
Journal Article 
Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery 
Tong, L 
2005 
Yes 
Cellular and Molecular Life Sciences (CMLS)
ISSN: 1420-682X
EISSN: 1420-9071 
62 
16 
1784-1803 
English 
Acetyl-coenzyme A carboxylases (ACCs) have crucial roles in fatty acid metabolism in most living organisms. Mice deficient in ACC2 have continuous fatty acid oxidation and reduced body fat and body weight, validating this enzyme as a target for drug development against obesity, diabetes and other symptoms of the metabolic syndrome. ACC is a biotin-dependent enzyme and catalyzes the carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase (BC) and carboxyltransferase (CT). ACC is a multi-subunit enzyme in most prokaryotes, whereas it is a large, multi-domain enzyme in most eukaryotes. The activity of the enzyme can be controlled at the transcriptional level as well as by small molecule modulators and covalent modification. This review will summarize the structural information that is now available for both the BC and CT enzymes, as well as the molecular mechanism of action of potent ACC inhibitors. The current intense research on these enzymes could lead to the development of novel therapies against metabolic syndrome and other diseases. 
metabolic syndrome; obesity; diabetes; structure-based drug design; fatty acid metabolism; protein structure and function; biotin-dependent; carboxylases; enzyme catalysis and mechanism; activated protein-kinase; fatty-acid synthesis; alopecurus-myosuroides; huds.; element-binding protein-1; coa-carboxylase; biotin carboxylase; crystal-structure; black-grass; carboxyltransferase domain; escherichia-coli