InterPro domain: IPR010259

Proteinase propeptide inhibitors (sometimes refered to as activation peptides) are responsible for the modulation of folding and activity of the pro-enzyme or zymogen. The pro-segment docks into the enzyme moiety shielding the substrate binding site, thereby promoting inhibition of the enzyme. Several such propeptides share a similar topology [ 1 ], despite often low sequence identities [ 2 ]. The propeptide region has an open-sandwich antiparallel-alpha/antiparallel-beta fold, with two alpha-helices and four beta-strands with a (beta/alpha/beta)x2 topology.

This entry represents the propeptide domain at the N terminus of peptidases belonging to MEROPS family S8A, subtilisins. The subtilisin propeptides are known to function as molecular chaperones, assisting in the folding of the mature peptidase [ 3 ]. The propeptide is removed by proteolytic cleavage; removal activating the enzyme. This domain is also found in members of MEROPS proteinase inhibitor family I9.

1. Solution structure of the pro-hormone convertase 1 pro-domain from Mus musculus. J. Mol. Biol. 320, 801-12
2. The crystal structure of an autoprocessed Ser221Cys-subtilisin E-propeptide complex at 2.0 A resolution. J. Mol. Biol. 284, 137-44
3. Functional analysis of the propeptide of subtilisin E as an intramolecular chaperone for protein folding. Refolding and inhibitory abilities of propeptide mutants. J. Biol. Chem. 270, 25127-32