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Volume 271, Number 45, Issue of November 8, 1996 pp. 28422-28429
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

Structure-Function Relationships of the Saccharomyces cerevisiae Fatty Acid Synthase
THREE-DIMENSIONAL STRUCTURE

(Received for publication, July 11, 1996, and in revised form, August 26, 1996)

Steven J. Kolodziej Dagger , Pawel A. Penczek § , John P. Schroeter Dagger and James K. Stoops Dagger

From the Dagger  Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston, Texas 77030, and § Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany, New York 12201

The three-dimensional structure of the Saccharomyces cerevisie fatty acid synthase was computed from electron microscopy of stain images. The barrel-shaped structure (point group symmetry 32) has major and minor axes of ~245 × 220 Å, respectively, and consists of two different subunits organized in an alpha 6beta 6 complex (Mr = 2.5 × 106). Two sets of three beta subunits form triangle-shaped caps that enclose the ends of the barrel. The wall of the barrel appears to consist of three N-shaped alpha subunit pairs each with an over and underlying arch-shaped beta subunit. Inside the molecule there are three major interconnected cavities that are tilted ~20° with respect to its major axis. An axle-shaped structure extends the length of the cavity on the 3-fold axis and is connected to the two ends of the barrel. The cavities are partially divided on the equator of the molecule by three spokes that extend from the axle on the 2-fold axis to the exterior wall. We propose that these six cavities constitute the six equivalent sites of fatty acid synthesis resulting in an extraordinary structure-function relationship with the 42 catalytic sites involved in fatty acid synthesis inside the molecule. The six cavities each have two funnel-shaped openings (~20 Å in diameter) which may serve to permit the diffusion of substrates and products in and out of these functional units. The subunits appear to be arranged in a manner that affords extensive intermolecular interactions contributing to the stability of this macromolecular complex.


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