Structure-function relationships of the Saccharomyces cerevisiae fatty acid synthase. Three-dimensional structure

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Biology

Background:

• Fatty acid synthase (FAS) is a crucial multienzyme complex responsible for de novo fatty acid biosynthesis.
• Understanding the structural organization of FAS is key to elucidating its catalytic mechanisms and regulation.

Purpose of the Study:

• To determine the three-dimensional structure of Saccharomyces cerevisiae fatty acid synthase.
• To investigate the relationship between the complex's structure and its function in fatty acid synthesis.

Main Methods:

• Computation of the three-dimensional structure using electron microscopy of stain images.
• Analysis of the subunit organization and internal cavities.

Main Results:

• The structure is a barrel-shaped alpha6beta6 complex with approximate dimensions of 245 x 220 A.
• Two sets of beta subunits form caps, and the barrel wall comprises alpha and beta subunits.
• Three interconnected cavities, tilted relative to the major axis, are present internally.
• An axle-shaped structure runs along the 3-fold axis, connected to the barrel ends.
• Six funnel-shaped openings (approx. 20 A diameter) facilitate substrate/product diffusion.
• The complex exhibits extensive intermolecular interactions, ensuring stability.

Conclusions:

• The six internal cavities are proposed as the functional sites for fatty acid synthesis.
• The structure-function relationship is highlighted, with 42 catalytic sites located within the molecule.
• The arrangement of subunits and internal cavities supports efficient fatty acid biosynthesis.