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Crystal Structure of the Carboxyltransferase Domain of Acetyl-Coenzyme A Carboxylase

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Science  28 Mar 2003:
Vol. 299, Issue 5615, pp. 2064-2067
DOI: 10.1126/science.1081366

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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.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: tong{at}como.bio.columbia.edu

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