1uyr
From Proteopedia
ACETYL-COA CARBOXYLASE CARBOXYLTRANSFERASE DOMAIN IN COMPLEX WITH INHIBITOR DICLOFOP
Overview
Acetyl-CoA carboxylases (ACCs) are crucial for the metabolism of fatty acids, making these enzymes important targets for the development of therapeutics against obesity, diabetes, and other diseases. The carboxyltransferase (CT) domain of ACC is the site of action of commercial herbicides, such as haloxyfop, diclofop, and sethoxydim. We have determined the crystal structures at up to 2.5-A resolution of the CT domain of yeast ACC in complex with the herbicide haloxyfop or diclofop. The inhibitors are bound in the active site, at the interface of the dimer of the CT domain. Unexpectedly, inhibitor binding requires large conformational changes for several residues in this interface, which create a highly conserved hydrophobic pocket that extends deeply into the core of the dimer. Two residues that affect herbicide sensitivity are located in this binding site, and mutation of these residues disrupts the structure of the domain. Other residues in the binding site are strictly conserved among the CT domains.
About this Structure
1UYR is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
Reference
Molecular basis for the inhibition of the carboxyltransferase domain of acetyl-coenzyme-A carboxylase by haloxyfop and diclofop., Zhang H, Tweel B, Tong L, Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5910-5. Epub 2004 Apr 12. PMID:15079078 Page seeded by OCA on Sat May 3 11:52:37 2008
