The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix

Aspartic proteinase A from yeast is specifically and potently inhibited by a small protein called IA(3) from Saccharomyces cerevisiae. Although this i nhibitor consists of 68 residues, we show that the inhibitory activity resi des within the N-terminal half of the molecule. Structures solved at 2.2 an d 1.8 Angstrom, respectively, for complexes of proteinase A with full-lengt h IA(3) and with a truncated form consisting only of residues 2-34, reveal an unprecedented mode of inhibitor-enzyme interactions, Neither form of the free inhibitor has detectable intrinsic secondary structure in solution. H owever, upon contact with the enzyme, residues 2-32 become ordered and adop t a near-perfect alpha-helical conformation. Thus, the proteinase acts as a folding template, stabilizing the helical conformation in the inhibitor, w hich results in the potent and specific blockage of the proteolytic activit y.