3PGQ

Crystal Structure of the Carboxyltransferase Domain of S. cerevisiae Acetyl CoA Carboxylase in Complex with Pinoxaden

Summary for 3PGQ

• Entry DOI: 10.2210/pdb3pgq/pdb
• Related: 1OD4 1UYR 1UYS 1UYT 1UYV 3K8X
• Descriptor: Acetyl-CoA carboxylase, 8-(2-ethenyl-6-ethyl-4-methylphenyl)tetrahydro-7H-pyrazolo[1,2-d][1,4,5]oxadiazepine-7,9(8H)-dione (2 entities in total)
• Functional Keywords: transferase, carboxyltransferase, ligase
• Biological source: Saccharomyces cerevisiae (brewer's yeast,lager beer yeast,yeast)
• Total number of polymer chains: 3
• Total formula weight: 261062.21

Authors

Tong, L.,Yu, L.P.C.,Kim, Y.S. (deposition date: 2010-11-02, release date: 2010-12-22, Last modification date: 2024-02-21)

Primary citation

Yu, L.P.,Kim, Y.S.,Tong, L.
Mechanism for the inhibition of the carboxyltransferase domain of acetyl-coenzyme A carboxylase by pinoxaden.
Proc.Natl.Acad.Sci.USA, 107:22072-22077, 2010

PubMed Abstract: Acetyl-CoA carboxylases (ACCs) are crucial metabolic enzymes and have been targeted for drug development against obesity, diabetes, and other diseases. The carboxyltransferase (CT) domain of this enzyme is the site of action for three different classes of herbicides, as represented by haloxyfop, tepraloxydim, and pinoxaden. Our earlier studies have demonstrated that haloxyfop and tepraloxydim bind in the CT active site at the interface of its dimer. However, the two compounds probe distinct regions of the dimer interface, sharing primarily only two common anchoring points of interaction with the enzyme. We report here the crystal structure of the CT domain of yeast ACC in complex with pinoxaden at 2.8-Å resolution. Despite their chemical diversity, pinoxaden has a similar binding mode as tepraloxydim and requires a small conformational change in the dimer interface for binding. Crystal structures of the CT domain in complex with all three classes of herbicides confirm the importance of the two anchoring points for herbicide binding. The structures also provide a foundation for understanding the molecular basis of the herbicide resistance mutations and cross resistance among the herbicides, as well as for the design and development of new inhibitors against plant and human ACCs.

PubMed: 21135213
DOI: 10.1073/pnas.1012039107

Experimental method

X-RAY DIFFRACTION (2.8 Å)