Conformational flexibility of metazoan fatty acid synthase enables catalysis.

ABSTRACT: The metazoan cytosolic fatty acid synthase (FAS) contains all of the enzymes required for de novo fatty acid biosynthesis covalently linked around two reaction chambers. Although the three-dimensional architecture of FAS has been mostly defined, it is unclear how reaction intermediates can transfer between distant catalytic domains. Using single-particle EM, we have identified a near continuum of conformations consistent with a remarkable flexibility of FAS. The distribution of conformations was influenced by the presence of substrates and altered by different catalytic mutations, suggesting a direct correlation between conformation and specific enzymatic activities. We interpreted three-dimensional reconstructions by docking high-resolution structures of individual domains, and they show

SUBMITTER: Brignole EJ 

PROVIDER: S-EPMC2653270 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature