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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 themost complex cellular multienzymes, in that each 270-kilodaltonpolypeptide chain carries all seven functional domains requiredfor fatty acid synthesis. We have calculated a 4.5 angstrom–resolutionx-ray crystallographic map of porcine fatty acid synthase, highlyhomologous to the human multienzyme, and placed homologous templatestructures of all individual catalytic domains responsible forthe cyclic elongation of fatty acid chains into the electrondensity. The positioning of domains reveals the complex architectureof the multienzyme forming an intertwined dimer with two lateralsemicircular reaction chambers, each containing a full set ofcatalytic domains required for fatty acid elongation. Largedistances between active sites and conformational differencesbetween the reaction chambers demonstrate that mobility of theacyl carrier protein and general flexibility of the multienzymemust accompany handover of the reaction intermediates duringthe 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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