3pgq
From Proteopedia
Crystal Structure of the Carboxyltransferase Domain of S. cerevisiae Acetyl CoA Carboxylase in Complex with Pinoxaden
Structural highlights
Function[ACAC_YEAST] Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in the synthesis of very-long-chain fatty acid synthesis which is required to maintain a functional nuclear envelope. Required for acylation and vacuolar membrane association of VAC8 which is necessary to maintain a normal morphology of the vacuole.[1] [2] [3] [4] [5] Publication Abstract from PubMedAcetyl-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-A 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. Mechanism for the inhibition of the carboxyltransferase domain of acetyl-coenzyme A carboxylase by pinoxaden.,Yu LP, Kim YS, Tong L Proc Natl Acad Sci U S A. 2010 Dec 6. PMID:21135213[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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