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Expression, purification and characterization of a Kunitz‐type protease inhibitor domain from human amyloid precursor protein homolog
Author(s) -
Petersen Lars C.,
Bjørn Søren E.,
Norris Fanny,
Norris Kjeld,
Sprecher Cindy,
Foster Donald C.
Publication year - 1994
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(94)80115-0
Subject(s) - proteases , serine protease , amyloid precursor protein , protease inhibitor (pharmacology) , trypsin inhibitor , chemistry , kallikrein , biochemistry , trypsin , serine , protease , serine proteinase inhibitors , microbiology and biotechnology , chymotrypsin , plasmin , kunitz sti protease inhibitor , biology , enzyme , medicine , disease , pathology , alzheimer's disease , human immunodeficiency virus (hiv) , antiretroviral therapy , viral load , immunology
The Kunitz‐type protease inhibitor domain from a recently identified homolog of the Alzheimer amyloid precursor protein (APPH KPI) was expressed in yeast, purified and characterized. Its inhibition profile towards several serine proteases was studied and compared to that of APP KPI, the Kunitz domain from the Alzheimer amyloid precursor protein. APPH KPI was shown to inhibit proteases with trypsin‐like specificity with an inhibitor profile resembling that of the APP KPI domain. The KPI domains from APP and APPH inhibited trypsin ( K i = 0.02 nM), and plasma kallikrein ( K i = 86 nM) with approximal equal affinity. In comparison to APP KPI ( K i = 82 nM) the KPI domain of the homolog, APPH KPI, ( K i = 8.8 nM) was a more potent inhibitor of glandular kallikrein. APPH KPI was a less potent inhibitor of chymotrypsin than APP KPI ( K i = 78 nM as compared to K i = 6 nM), plasmin ( K i = 81 nM as compared to 42 nM), and factor XI a ( K i = 14 nM as compared to K i = 0.7 nM). The affinity of factor XI a for APPH KPI is sufficiently high to allow for an interaction in the blood. It is, however, well possible that the physiological protease ligand for the receptor‐like APPH protein has yet to be identified.