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Inhibition of furin by serpin Spn4A from Drosophila melanogaster
Author(s) -
Oley Mareke,
Letzel Matthias C.,
Ragg Hermann
Publication year - 2004
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.2004.10.003
Subject(s) - furin , serpin , drosophila melanogaster , gene isoform , endoplasmic reticulum , cleavage (geology) , biochemistry , enzyme , microbiology and biotechnology , biology , chemistry , gene , paleontology , fracture (geology)
The serpin gene Spn4 from Drosophila melanogaster encodes multiple isoforms with alternative reactive site loops (RSL). Here, we show that isoform Spn4A inhibits human furin with an apparent k assoc of 5.5 × 10 6 M −1 s −1 . The serpin forms SDS‐stable complexes with the enzyme and the RSL of Spn4A is cleaved C‐terminally to the sequence –Arg–Arg–Lys–Arg↓ in accord with the recognition/cleavage site of furin. Immunofluorescence studies show that Spn4A is localized in the endoplasmic reticulum (ER), suggesting that the inhibitor is an interesting tool for investigating the cellular mechanisms regulating furin and for the design of agents controlling prohormone convertases.