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 kassoc of 5.5 x 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.
Oley
Mareke
M
Department of Biotechnology, Faculty of Technology, University of Bielefeld, D-33501 Bielefeld, Germany.
Letzel
Matthias C
MC
Ragg
Hermann
H
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D017931:DNA Primers; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster; D045683:Furin / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000378:metabolism; D015843:Serpins / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism
D017931:DNA Primers; D029721:Drosophila Proteins; D011994:Recombinant Proteins; D015843:Serpins; C488721:Spn42Da protein, Drosophila; D045683:Furin