Autocatalytic activation of the furin zymogen requires removal of the emerging enzyme's N-terminus from the active site.

ABSTRACT:

Background

Before furin can act on protein substrates, it must go through an ordered process of activation. Similar to many other proteinases, furin is synthesized as a zymogen (profurin) which becomes active only after the autocatalytic removal of its auto-inhibitory prodomain. We hypothesized that to activate profurin its prodomain had to be removed and, in addition, the emerging enzyme's N-terminus had to be ejected from the catalytic cleft.

Methodology/principal findings

We constructed and analyzed the profurin mutants in which the egress of the emerging enzyme's N-terminus from the catalytic cleft was restricted. Mutants were autocatalytically processed at only the primary cleavage site Arg-Thr-Lys-Arg(107) downward arrowAsp(108), but not at both the primary and the sec

SUBMITTER: Gawlik K 

PROVIDER: S-EPMC2662429 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature