Structure of a dehydratase-isomerase from the bacterial pathway for biosynthesis of unsaturated fatty acids
Abstract
One enzyme plays a key role in the biosynthesis of virtually all unsaturated fatty acids in E. coli. $\beta$-Hydroxydecanoyl thioester dehydrase (dehydrase) shunts a ten-carbon intermediate in the biosynthetic pathway of saturated fatty acids into unsaturated products. It is a 38 kD homodimer that catalyzes two reactions: (1) the dehydration of (R)-3-hydroxydecanoyl-ACP and (2) the inter conversion of trans-2-decenoyl-ACP and cis-3-decenoyl-ACP. 2.0 A resolution crystal structures of free dehydrase, and the enzyme modified by its classic, mechanism-based inactivator, 3-decynoyl-NAC, have been determined. As the first high resolution structure of a fatty acid biosynthetic enzyme, the unique topology of the protein fold and the identification of the active site components reveal features of predictive value for another such enzyme, FabZ, which is postulated to be the nonspecific dehydratase involved in fatty acyl chain elongation. The active site is shared between the two subunits of the enzyme, and is completely isolated from the general solvent. A positively charged area surrounding the entrance to this tunnel, which could interact with the negatively charged ACP, was also found.
Degree
Ph.D.
Advisors
Smith, Purdue University.
Subject Area
Biophysics|Biochemistry|Molecular biology
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