Inhibition of furin by serpin Spn4A from Drosophila melanogaster

Oley M, Letzel M, Ragg H. Inhibition of furin by serpin Spn4A from Drosophila melanogaster. FEBS Letters. 2004;577(1-2):165-169.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 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-Argdown arrow 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. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved