Crystal Structure of the Carboxyltransferase Domain of Acetyl-Coenzyme A Carboxylase
Top Cited Papers
- 28 March 2003
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 299 (5615) , 2064-2067
- https://doi.org/10.1126/science.1081366
Abstract
Acetyl–coenzyme A carboxylases (ACCs) are required for the biosynthesis and oxidation of long-chain fatty acids. They are targets for therapeutics against obesity and diabetes, and several herbicides function by inhibiting their carboxyltransferase (CT) domain. We determined the crystal structure of the free enzyme and the coenzyme A complex of yeast CT at 2.7 angstrom resolution and found that it comprises two domains, both belonging to the crotonase/ClpP superfamily. The active site is at the interface of a dimer. Mutagenesis and kinetic studies reveal the functional roles of conserved residues here. The herbicides target the active site of CT, providing a lead for inhibitor development against human ACCs.Keywords
This publication has 24 references indexed in Scilit:
- The Carboxyltransferase Activity of the Apicoplast Acetyl-CoA Carboxylase of Toxoplasma gondii Is the Target of Aryloxyphenoxypropionate InhibitorsPublished by Elsevier ,2002
- Competing protein:protein interactions are proposed to control the biological switch of the E coli biotin repressorProtein Science, 2001
- Bacterial Fatty Acid Biosynthesis: Targets for Antibacterial Drug DiscoveryAnnual Review of Microbiology, 2001
- The crystal structure of Δ3-Δ2-enoyl-CoA isomeraseJournal of Molecular Biology, 2001
- Continuous Fatty Acid Oxidation and Reduced Fat Storage in Mice Lacking Acetyl-CoA Carboxylase 2Science, 2001
- New Reactions in the Crotonase Superfamily: Structure of Methylmalonyl CoA Decarboxylase from Escherichia coli,Biochemistry, 2000
- The Mitochondrial Carnitine Palmitoyltransferase System — From Concept to Molecular AnalysisEuropean Journal of Biochemistry, 1997
- Determination of Macromolecular Structures from Anomalous Diffraction of Synchrotron RadiationScience, 1991
- Ribbon models of macromoleculesJournal of Molecular Graphics, 1987
- FATTY ACID SYNTHESIS AND ITS REGULATIONAnnual Review of Biochemistry, 1983