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Architecture of a Fungal Fatty Acid Synthase at 5 Å Resolution
Simon Jenni,*Marc Leibundgut,*Timm Maier,Nenad Ban
All steps of fatty acid synthesis in fungi are catalyzed bythe fatty acid synthase, which forms a 2.6-megadalton 6ß6complex. We have determined the molecular architecture of thismultienzyme by fitting the structures of homologous enzymesthat catalyze the individual steps of the reaction pathway intoa 5 angstrom x-ray crystallographic electron density map. Thehuge assembly contains two separated reaction chambers, eachequipped with three sets of active sites separated by distancesup to 130 angstroms, across which acyl carrier protein shuttlessubstrates during the reaction cycle. Regions of the electrondensity arising from well-defined structural features outsidethe catalytic domains separate the two reaction chambers andserve as a matrix in which domains carrying the various activesites are embedded. The structure rationalizes the compartmentalizationof fatty acid synthesis, and the spatial arrangement of theactive sites has specific implications for our understandingof the reaction cycle mechanism and of the architecture of multienzymesin general.
Institute of Molecular Biology and Biophysics, Department of Biology, Swiss Federal Institute of Technology (ETH Zurich), 8093 Zurich, Switzerland.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: ban{at}mol.biol.ethz.ch
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Mass Spectrometry-Based Systems Approach for Identification of Inhibitors of Plasmodium falciparum Fatty Acid Synthase.
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Structure of Fungal Fatty Acid Synthase and Implications for Iterative Substrate Shuttling.
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Identification of a starter unit acyl-carrier protein transacylase domain in an iterative type I polyketide synthase.
J. M. Crawford, B. C. R. Dancy, E. A. Hill, D. W. Udwary, and C. A. Townsend (2006)
PNAS
103, 16728-16733
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Conformational switches modulate protein interactions in peptide antibiotic synthetases..
A. Koglin, M. R. Mofid, F. Lohr, B. Schafer, V. V. Rogov, M.-M. Blum, T. Mittag, M. A. Marahiel, F. Bernhard, and V. Dotsch (2006)
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312, 273-276
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Architecture of Mammalian Fatty Acid synthase at 4.5 a resolution..
6ß6 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 
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. 
To whom correspondence should be addressed. E-mail: 
