1DP5

THE STRUCTURE OF PROTEINASE A COMPLEXED WITH A IA3 MUTANT INHIBITOR

Summary for 1DP5

• Entry DOI: 10.2210/pdb1dp5/pdb
• Descriptor: PROTEINASE A, PROTEINASE INHIBITOR IA3, beta-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: proteinase a, mmm, ia3 mutant, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Total number of polymer chains: 2
• Total formula weight: 45060.45

Authors

Li, M.,Phylip, H.L.,Lees, W.E.,Winther, J.R.,Dunn, B.M.,Wlodawer, A.,Kay, J.,Guschina, A. (deposition date: 1999-12-23, release date: 2000-05-03, Last modification date: 2024-10-16)

Primary citation

Li, M.,Phylip, L.H.,Lees, W.E.,Winther, J.R.,Dunn, B.M.,Wlodawer, A.,Kay, J.,Gustchina, A.
The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix.
Nat.Struct.Biol., 7:113-117, 2000

PubMed Abstract: 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.

PubMed: 10655612
DOI: 10.1038/72378

Experimental method

X-RAY DIFFRACTION (2.2 Å)