Extended Data Fig. 10: Cartoon representation of the proposed mechanism of ceramide synthases and their inhibition by FB1.
From: Structural basis of the mechanism and inhibition of a human ceramide synthase
a, CerS6 initially reacts with an acyl-CoA substrate, forming a covalent acyl-enzyme intermediate and releasing CoA as the first product. Subsequently, the reaction of the acyl-enzyme intermediate with sphinganine produces ceramide as the final product. Ceramide dissociates from the enzyme, which can then react with another acyl-CoA substrate to re-start the cycle. b, Reaction of the covalent acyl-enzyme intermediate species with FB1 results in the formation of an N-acyl FB1 product. This inhibitory product remains tightly bound in the central cavity, forming polar interactions near the cytoplasmic entrance, and preventing recycling of the enzyme.
