The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix
The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix
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DOI：
10.1038/72378
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发表时间：
2000-02-01
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影响因子：
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通讯作者：
Gustchina, A
中科院分区：
文献类型：
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作者：
Li, M;Phylip, LH;Gustchina, A
酵母中的天冬氨酸蛋白酶 A 可被酿酒酵母中称为 IA(3) 的小蛋白特异性且有效地抑制。尽管该抑制剂由 68 个残基组成，但我们表明抑制活性位于该分子的 N 末端一半。蛋白酶 A 与全长 IA(3) 和仅由残基 2-34 组成的截短形式的复合物的结构分别在 2.2 和 1.8 埃处解析，揭示了前所未有的抑制剂-酶相互作用模式，两种形式的游离抑制剂在溶液中都没有可检测到的内在二级结构。然而，在与酶接触后，残基 2-32 变得有序并采用近乎完美的 α 螺旋构象。因此，蛋白酶充当折叠模板，稳定抑制剂中的螺旋构象，从而有效且特异性地阻断蛋白水解活性。
Aspartic proteinase A from yeast is specifically and potently inhibited by a small protein called IA(3) 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 Angstrom, respectively, for complexes of proteinase A with full-length 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. 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.