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 Ki, respectively.
Chen
Y
Y
Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec, Canada.
Plouffe
C
C
Ménard
R
R
Storer
A C
AC
D000409:Alanine / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002401:Cathepsin B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003374:Coumarins / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats
D003374:Coumarins; D004151:Dipeptides; D010446:Peptide Fragments; D011498:Protein Precursors; C021159:benzyloxycarbonyl-phenylalanylarginine-4-methylcoumaryl-7-amide; D002401:Cathepsin B; D000409:Alanine