1G0V

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

1G0V の概要

• エントリーDOI: 10.2210/pdb1g0v/pdb
• 関連するPDBエントリー: 1DP5 1DPJ
• 分子名称: 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)
• 機能のキーワード: proteinase a, mvv, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40967.94

構造登録者

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. (登録日: 2000-10-09, 公開日: 2001-04-21, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2 Å)