title: Cathepsin D inactivates cysteine proteinase inhibitors, cystatins.
abstract: The formation of inactive complexes in excess molar amounts of human cathepsins H and L with their protein inhibitors human stefin A, human stefin B and chicken cystatin at pH 5.6 has been shown by measurement of enzyme activity coupled with reverse-phase HPLC not to involve covalent cleavage of the inhibitors. Inhibition must be the direct result of binding. On the contrary the interaction of cystatins with aspartic proteinase cathepsin D at pH 3.5 for 60 min followed by HPLC resulted in their inactivation accompanied by peptide bond cleavage at several sites, preferentially those involving hydrophobic amino acid residues. The released peptides do not inhibit papain and cathepsin L. These results explain reported elevated levels of cysteine proteinases and lead to the proposal that cathepsin D exerts an important function, through inactivation of cystatins, in the increased activities of cysteine proteinases in human diseases including muscular distrophy.
authors.affiliation: Department of Biochemistry, J. Stefan Institute, Ljubljana, Yugoslavia.
authors.forename: B
authors.initials: B
authors.lastname: Lenarcic
authors.forename: J
authors.initials: J
authors.lastname: Kos
authors.forename: I
authors.initials: I
authors.lastname: Dolenc
authors.forename: P
authors.initials: P
authors.lastname: Lucovnik
authors.forename: I
authors.initials: I
authors.lastname: Krizaj
authors.forename: V
authors.initials: V
authors.lastname: Turk
mesh_terms: D000595:Amino Acid Sequence; D002402:Cathepsin D / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D055313:Cystatin B; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D006801:Humans; D008969:Molecular Sequence Data; D011480:Protease Inhibitors; D011506:Proteins / Q000037:antagonists & inhibitors*
chemical_list: C524994:CSTB protein, human; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D011480:Protease Inhibitors; D011506:Proteins; C100158:cystatin, egg-white; D055313:Cystatin B; D002402:Cathepsin D