Céline Plouffe

Delineating functionally important regions and residues in the cathepsin B propeptide for inhibitory activity.

Synthetic peptides derived from the proregion of rat cathepsin B were used to identify functionally important regions and residues for cathepsin B inhibition. Successive 5 amino acid deletions of a 56 amino acid propeptide from both the N‐ and C‐termini has allowed the identification of two regions important for inhibitory activity: the NTTWQ (residues 21p–25p) and CGTVL (42p–46p) regions. Alanine scanning of residues within these two regions indicates that Trp‐24p and Cys‐42p contribute strongly to inhibition, their replacement by Ala resulting in 160‐ and 140‐fold increases in K i , respectively.