Journal of Biological Chemistry
Volume 273, Issue 4, 23 January 1998, Pages 1851-1854
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Inhibition of Soluble Recombinant Furin by Human Proteinase Inhibitor 8*

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Furin is a ubiquitous prototypical mammalian kexin/subtilisin-like endoproteinase that is involved in the proteolytic processing of a variety of proteins in the exocytic and endocytic pathways, with cleavage occurring at the C terminus of the minimal consensus furin recognition sequence Arg-Xaa-Xaa-Arg. In this study, human proteinase inhibitor 8 (PI8), a widely expressed 45-kDa ovalbumin-type serpin that contains two sequences homologous to the minimal sequence for recognition by furin in its reactive site loop, was tested for its ability to inhibit a recombinant soluble form of human furin. PI8 formed an SDS-stable complex with furin and inhibited its amidolytic activity via a two-step mechanism with ak assoc of 6.5 × 105m−1 s−1 and an overallK i of 53.8 pm. Thus, PI8 inhibits furin in a rapid, tight binding manner that is characteristic of physiological serpin-proteinase interactions. PI8 is not only the first human ovalbumin-type serpin to demonstrate inhibitory activity toward furin, but it is also the first significant inhibitor of furin identified that is not a serpin reactive site loop mutant, either naturally occurring or engineered.

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This work was supported in part by National Institutes of Health Research Grant HL35246 (to W. K.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.