Architecture of mammalian fatty acid synthase at 4.5 A resolution.
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.
Maier
Timm
T
Institute of Molecular Biology and Biophysics, Department of Biology, Swiss Federal Institute of Technology (ETH Zurich), 8093 Zurich, Switzerland.
Jenni
Simon
S
Ban
Nenad
N
D000213:Acyl Carrier Protein / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D003460:Crystallization; D018360:Crystallography, X-Ray; D019281:Dimerization; D064429:Fatty Acid Synthases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis; D008321:Mammary Glands, Animal / Q000201:enzymology; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry; D013552:Swine
D000213:Acyl Carrier Protein; D005227:Fatty Acids; D021122:Protein Subunits; D064429:Fatty Acid Synthases