Expression, purification and characterization of a Kunitz‐type protease inhibitor domain from human amyloid precursor protein homolog

FEBS Letters

Petersen, Lars C.¹  Sprecher, Cindy²  Norris, Fanny¹  Bjørn, Søren E.¹  Foster, Donald C.²  Norris, Kjeld¹ 

[1] Novo Nordisk Research Institute, Novo Nordisk A/S, Niels Steensens Vej 1, DK-2820 Gentofte, Denmark;ZymoGenetics Inc., 4225 Roosevelt Way NE, Seattle, WA 98105, USA

关键词: Amyloid precursor protein homolog;    Kunitz-type protease inhibitor;    Factor XIa;    Alzheimer;    Serine protease;    APP;    amyloid precursor protein;    APPH;    amyloid precursor protein homolog;    KPI;    Kunitz-type protease inhibitor;    BPTI;    bovine pancreatic trypsin inhibitor;   

DOI  :  10.1016/0014-5793(94)80115-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown