Architecture of a fungal fatty acid synthase at 5 A resolution.
All steps of fatty acid synthesis in fungi are catalyzed by the fatty acid synthase, which forms a 2.6-megadalton alpha6beta6 complex. We have determined the molecular architecture of this multienzyme by fitting the structures of homologous enzymes that catalyze the individual steps of the reaction pathway into a 5 angstrom x-ray crystallographic electron density map. The huge assembly contains two separated reaction chambers, each equipped with three sets of active sites separated by distances up to approximately 130 angstroms, across which acyl carrier protein shuttles substrates during the reaction cycle. Regions of the electron density arising from well-defined structural features outside the catalytic domains separate the two reaction chambers and serve as a matrix in which domains carrying the various active sites are embedded. The structure rationalizes the compartmentalization of fatty acid synthesis, and the spatial arrangement of the active sites has specific implications for our understanding of the reaction cycle mechanism and of the architecture of multienzymes in general.
Jenni
Simon
S
Institute of Molecular Biology and Biophysics, Department of Biology, Swiss Federal Institute of Technology (ETH Zurich), 8093 Zurich, Switzerland.
Leibundgut
Marc
M
Maier
Timm
T
Ban
Nenad
N
D000213:Acyl Carrier Protein / Q000737:chemistry / Q000378:metabolism; D001203:Ascomycota / Q000201:enzymology*; 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; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D000213:Acyl Carrier Protein; D005227:Fatty Acids; D064429:Fatty Acid Synthases