Inhibition of furin by serpin Spn4A from Drosophila melanogaster

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 i...

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Bibliographic Details
Published in:FEBS letters 2004-11, Vol.577 (1), p.165-169
Main Authors: Oley, Mareke, Letzel, Matthias C., Ragg, Hermann
Format: Article
Language:English
Subjects:
Animals
Base Sequence
COS Cells
DNA Primers
Drosophila melanogaster
Drosophila Proteins - physiology
Endoplasmic reticulum
ER, endoplasmic reticulum
Furin
Furin - antagonists & inhibitors
GST, glutathione S-transferase
PBS, phosphate buffered saline
PDI, protein disulfide isomerase
Protease inhibitor
Recombinant Proteins - metabolism
RSL, reactive site loop
Serpin
Serpins - physiology
SI, stoichiometry of inhibition
Subcellular Fractions - metabolism
TEV, tobacco etch virus
α1-PDX, α1-antitrypsin Portland
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Summary: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.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2004.10.003