Figure 5

Model of cucurbitacin binding to Cofilin1. A) Reaction of cucurbitacin E (Michaels acceptor group in red) with nucleophilic thiol, producing a product that conserves mass. B) Crystal structure of human Cofilin1 (space filled) modelled with associated actin (ribbon), based on the C-terminal Cofilin-like domain of mouse twinfilin (Twf-C) in complex with actin. Cucurbitacin E (sticks) is modelled as conjugated to Cys139, with its potential rotational space illustrated by the transparent yellow sphere. The size of cucurbitacin E at this position would likely clash with actin, resulting in reduced actin-severing activity.