The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix
Research output: Contribution to journal › Journal article › Research › peer-review
Aspartic proteinase A from yeast is specifically and potently inhibited by a small protein called IA3 from Saccharomyces cerevisiae. Although this inhibitor consists of 68 residues, we show that the inhibitory activity resides within the N-terminal half of the molecule. Structures solved at 2.2 and 1.8 A, respectively, for complexes of proteinase A with full-length IA3 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. However, upon contact with the enzyme, residues 2-32 become ordered and adopt a near-perfect alpha-helical conformation. Thus, the proteinase acts as a folding template, stabilizing the helical conformation in the inhibitor, which results in the potent and specific blockage of the proteolytic activity.
Original language | English |
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Journal | Nature Structural & Molecular Biology |
Volume | 7 |
Issue number | 2 |
Pages (from-to) | 113-117 |
Number of pages | 5 |
ISSN | 1545-9993 |
DOIs | |
Publication status | Published - 2000 |
Externally published | Yes |
- Amino Acid Sequence, Aspartic Acid Endopeptidases, Circular Dichroism, Crystallography, X-Ray, Fungal Proteins, Hydrogen-Ion Concentration, Methionine, Models, Molecular, Molecular Sequence Data, Mutation, Protein Conformation, Protein Folding, Recombinant Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Trypsin
Research areas
ID: 43973904