CTSL and malaria: The model identified potential interactions between the inhibitory portion of the prodomain and mature falcipain-2 that appear to explain the inhibitory activity, and also the ability of the prodomain of falcipain-2, but not that of the related protease cathepsin L, to inhibit cathepsin B. Taken together, our results identify and structurally characterize a minimum inhibitory domain of the falcipain-2 prodomain, offering a starting point for new considerations for the inhibition of key proteases of malaria parasites.