Crystal structure of ß-ketoacyl-acyl carrier protein synthase II from E.coli reveals the molecular architecture of condensing enzymes.

In the biosynthesis of fatty acids, the β-ketoacylacyl carrier protein (ACP) synthases catalyze chain elongation by the addition of two-carbon units derived from malonyl-ACP to an acyl group bound to either ACP or CoA. The crystal structure of β-ketoacyl synthase II from Escherichia coli has been determined with the multiple isomorphous replacement method and refined at 2.4 Å resolution. The subunit consists of two mixed five-stranded β-sheets surrounded by α-helices. The two sheets are packed against each other in such a way that the fold can be described as consisting of five layers, α­β­α­β­α. The enzyme is a homodimer, and the subunits are related by a crystallographic 2-fold axis. The two active sites are located near the dimer interface but are ∼25 Å apart. The proposed nucleophile in the reaction, Cys163, is located at the bottom of a mainly hydrophobic pocket which is also lined with several conserved polar residues. In spite of very low overall sequence homology, the structure of β-ketoacyl synthase is similar to that of thiolase, an enzyme involved in the β-oxidation pathway, indicating that both enzymes might have a common ancestor. [ABSTRACT FROM AUTHOR]