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Inhibition of human matriptase by eglin c variants
Author(s) -
Désilets Antoine,
Longpré Jean-Michel,
Beaulieu Marie-Ève,
Leduc Richard
Publication year - 2006
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/j.febslet.2006.03.030
Subject(s) - serine protease , transmembrane protein , microbiology and biotechnology , protease , serine , chemistry , enzyme , protease inhibitor (pharmacology) , biology , biochemistry , receptor , genetics , virus , antiretroviral therapy , viral load
Based on the enzyme specificity of matriptase, a type II transmembrane serine protease (TTSP) overexpressed in epithelial tumors, we screened a cDNA library expressing variants of the protease inhibitor eglin c in order to identify potent matriptase inhibitors. The most potent of these, R 1 K 4 ′‐eglin, which had the wild‐type Pro 45 (P1 position) and Tyr 49 (P4′ position) residues replaced with Arg and Lys, respectively, led to the production of a selective, high affinity ( K i of 4 nM) and proteolytically stable inhibitor of matriptase. Screening for eglin c variants could yield specific, potent and stable inhibitors to matriptase and to other members of the TTSP family.