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Science 3 March 2006:
Vol. 311. no. 5765, pp. 1258 - 1262
DOI: 10.1126/science.1123248
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Research Articles

Architecture of Mammalian Fatty Acid Synthase at 4.5 Å Resolution

Timm Maier, Simon Jenni, Nenad Ban*

The homodimeric mammalian fatty acid synthase is one of the most complex cellular multienzymes, in that each 270-kilodalton polypeptide chain carries all seven functional domains required for fatty acid synthesis. We have calculated a 4.5 angstrom–resolution x-ray crystallographic map of porcine fatty acid synthase, highly homologous to the human multienzyme, and placed homologous template structures of all individual catalytic domains responsible for the cyclic elongation of fatty acid chains into the electron density. The positioning of domains reveals the complex architecture of the multienzyme forming an intertwined dimer with two lateral semicircular reaction chambers, each containing a full set of catalytic domains required for fatty acid elongation. Large distances between active sites and conformational differences between the reaction chambers demonstrate that mobility of the acyl carrier protein and general flexibility of the multienzyme must accompany handover of the reaction intermediates during the reaction cycle.

Institute of Molecular Biology and Biophysics, Department of Biology, Swiss Federal Institute of Technology (ETH Zurich), 8093 Zurich, Switzerland.

* To whom correspondence should be addressed. E-mail: ban{at}mol.biol.ethz.ch

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