1G0V

THE STRUCTURE OF PROTEINASE A COMPLEXED WITH A IA3 MUTANT, MVV

Summary for 1G0V

• Entry DOI: 10.2210/pdb1g0v/pdb
• Related: 1DP5 1DPJ
• Descriptor: PROTEINASE A, PROTEASE A INHIBITOR 3, beta-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: proteinase a, mvv, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Saccharomyces cerevisiae (baker's yeast)
• Total number of polymer chains: 2
• Total formula weight: 40967.94

Authors

Phylip, L.H.,Lees, W.,Brownsey, B.G.,Bur, D.,Dunn, B.M.,Winther, J.,Gustchina, A.,Li, M.,Copeland, T.,Wlodawer, A.,Kay, J. (deposition date: 2000-10-09, release date: 2001-04-21, Last modification date: 2024-10-30)

Primary citation

Phylip, L.H.,Lees, W.E.,Brownsey, B.G.,Bur, D.,Dunn, B.M.,Winther, J.R.,Gustchina, A.,Li, M.,Copeland, T.,Wlodawer, A.,Kay, J.
The potency and specificity of the interaction between the IA3 inhibitor and its target aspartic proteinase from Saccharomyces cerevisiae.
J.Biol.Chem., 276:2023-2030, 2001

PubMed Abstract: The yeast IA3 polypeptide consists of only 68 residues, and the free inhibitor has little intrinsic secondary structure. IA3 showed subnanomolar potency toward its target, proteinase A from Saccharomyces cerevisiae, and did not inhibit any of a large number of aspartic proteinases with similar sequences/structures from a wide variety of other species. Systematic truncation and mutagenesis of the IA3 polypeptide revealed that the inhibitory activity is located in the N-terminal half of the sequence. Crystal structures of different forms of IA3 complexed with proteinase A showed that residues in the N-terminal half of the IA3 sequence became ordered and formed an almost perfect alpha-helix in the active site of the enzyme. This potent, specific interaction was directed primarily by hydrophobic interactions made by three key features in the inhibitory sequence. Whereas IA3 was cut as a substrate by the nontarget aspartic proteinases, it was not cleaved by proteinase A. The random coil IA3 polypeptide escapes cleavage by being stabilized in a helical conformation upon interaction with the active site of proteinase A. This results, paradoxically, in potent selective inhibition of the target enzyme.

PubMed: 11042188
DOI: 10.1074/jbc.M008520200

Experimental method

X-RAY DIFFRACTION (2 Å)