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(Received for publication, July 11, 1996, and in revised form, August 26, 1996)
From the 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
Volume 271, Number 45,
Issue of November 8, 1996
pp. 28422-28429
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
THREE-DIMENSIONAL STRUCTURE
,
and
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
6
6 complex
(Mr = 2.5 × 106). Two sets of
three
subunits form triangle-shaped caps that enclose the ends of
the barrel. The wall of the barrel appears to consist of three N-shaped
subunit pairs each with an over and underlying arch-shaped
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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