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Science 28 March 2003:
Vol. 299. no. 5615, pp. 2064 - 2067
DOI: 10.1126/science.1081366
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Reports
Crystal Structure of the Carboxyltransferase Domain of Acetyl-Coenzyme A Carboxylase
Hailong Zhang,
Zhiru Yang,*
Yang Shen,*
Liang Tong
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.
Department of Biological Sciences, Columbia University, New York,
NY 10027, USA.
*
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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