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

Y Chen, C Plouffe, R Ménard, A C Storer

Index: FEBS Lett. 393(1) , 24-6, (1996)

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Abstract

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 Ki, respectively.