An active enzyme constructed from a 9-amino acid alphabet
An active enzyme constructed from a 9-amino acid alphabet
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DOI：
10.1074/jbc.m507210200
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发表时间：
2005-11-11
影响因子：
4.8
通讯作者：
Hilvert, D
中科院分区：
文献类型：
--
作者：
Walter, KU;Vamvaca, K;Hilvert, D
大自然使用一组20种氨基酸来产生具有复杂功能的蛋白质结构库。在这里，我们结合设计和选择，创造了一种完全由一组只有9个氨基酸组成的酶，可以拯救缺乏分支酸的营养缺陷型细胞。简化的蛋白质捕获了其天然对应物的关键结构特征，但似乎不太稳定，更灵活。一个显着减少的氨基酸字母表产生活性催化剂的潜力支持的概念，原始酶可能具有低的氨基酸多样性，并表明组合工程策略，如这里使用的，可以普遍应用于创建新的结构和功能的酶。
Nature employs a set of 20 amino acids to produce a repertoire of protein structures endowed with sophisticated functions. Here, we combined design and selection to create an enzyme composed entirely from a set of only 9 amino acids that can rescue auxotrophic cells lacking chorismate mutase. The simplified protein captures key structural features of its natural counterpart but appears to be somewhat less stable and more flexible. The potential of a dramatically reduced amino acid alphabet to produce an active catalyst supports the notion that primordial enzymes may have possessed low amino acid diversity and suggests that combinatorial engineering strategies, such as the one used here, may be generally applied to create enzymes with novel structures and functions.