Molecular basis for the inhibition of the carboxyltransferase domain of acetyl-coenzyme-A carboxylase by haloxyfop and diclofop

摘要: Acetyl-CoA carboxylases (ACCs) are crucial for the metabolism of fatty acids, making these enzymes important targets development therapeutics against obesity, diabetes, and other diseases. The carboxyltransferase (CT) domain ACC is site action commercial herbicides, such as haloxyfop, diclofop, sethoxydim. We have determined crystal structures at up to 2.5-A resolution CT yeast in complex with herbicide haloxyfop or diclofop. inhibitors bound active site, interface dimer domain. Unexpectedly, inhibitor binding requires large conformational changes several residues this interface, which create a highly conserved hydrophobic pocket that extends deeply into core dimer. Two affect sensitivity located mutation disrupts structure Other strictly among domains.