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Differences in specificity for the interactions of stefins A, B and D with cysteine proteinases
Author(s) -
Lenarčič Brigita,
Križaj Igor,
Žunec Petra,
Turk Vito
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00984-2
Subject(s) - cathepsin b , chemistry , cysteine proteinase inhibitors , cysteine , cathepsin , cathepsin o , biochemistry , cathepsin l , amino acid , papain , enzyme , microbiology and biotechnology , cathepsin h , stereochemistry , biology , apoptosis , programmed cell death , caspase
Four different stefin‐type cysteine proteinase inhibitors have been isolated from porcine thymus and skin. Amino acid sequence determination revealed the presence of stefin A and stefin B type inhibitors and two new inhibitors, designated as porcine stefin D1 and stefin D2. Stefin D1 was identified as PLCPI, an inhibitor recently characterized from porcine polymorphonuclear leukocytes [Lenarčič et al. (1993) FEBS Lett. 336, 289–292]. Stefin A is composed of 101 amino acids and has an M r of 11391 while stefin B contains 98 amino acids, has an M r of 11174 and is N‐terminally blocked. All inhibitors were found to be fast‐acting inhibitors of papain, cathepsin L and cathepsin S ( K i = 0.009–0.161 nM). Stefins A and B also bind tightly and rapidly to cathepsin H ( K i = 0.027 and 0.069 nM, respectively), while stefins D1 and D2 have been shown to be very poor inhibitors of cathepsin H ( K i = 102–150 nM). he decreased affinity of these inhibitors toward cathepsin B ( K i = 2–1700 nM) was shown to be mainly due to the low second order association rate constants. The presence of a highly negatively charged N‐terminus on stefin D1 constitutes a likely structural determinant of inhibitor specificity.