Structure of the complex between the antibiotic cerulenin and its target, beta-ketoacyl-acyl carrier protein synthase

In the biosynthesis of fatty acids, the beta-ketoacyl-acyl carrier protein (ACP) synthases catalyze chain elongation by the addition of two-carbon uni ts derived from malonyl-ACP to an acyl group bound to either ACP or CoA. Th e enzyme is a possible drug target for treatment of certain cancers and for tuberculosis. The crystal structure of the complex of the enzyme from Esch erichia coli, and the fungal mycotoxin cerulenin reveals that the inhibitor is bound in a hydrophobic pocket formed at the dimer interface. Cerulenin is covalently attached to the active site cysteine through its C2 carbon at om. The fit of the inhibitor to the active site is not optimal, and there i s thus room for improvement through structure based design.