α1 -Antitrypsin (α1 -AT) serves as an archetypal example for the serine proteinase inhibitor (serpin) protein family and has been used as a scaffold for protein engineering for >35 years. Techniques used to engineer α1 -AT include targeted mutagenesis, protein fusions, phage display, glycoengineering, and consensus protein design. The goals of engineering have also been diverse, ranging from understanding serpin structure-function relationships, to the design of more potent or more specific proteinase inhibitors with potential therapeutic relevance. Here we summarize the history of these protein engineering efforts, describing the techniques applied to engineer α1 -AT, specific mutants of interest, and providing an appended catalog of the >200 α1 -AT mutants published to date.

中文翻译：

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设计Serpinα1-抗胰蛋白酶：多种目标和技术。

α1-抗胰蛋白酶（α1-AT）是丝氨酸蛋白酶抑制剂（serpin）蛋白质家族的原型实例，并且已被用作蛋白质工程的支架，已有超过35年的历史。用于工程化α1-AT的技术包括靶向诱变，蛋白质融合，噬菌体展示，糖工程和共有蛋白质设计。工程的目标也多种多样，从了解丝氨酸蛋白酶抑制剂结构-功能关系到设计具有潜在治疗意义的更有效或更具体的蛋白酶抑制剂。在这里，我们总结了这些蛋白质工程研究的历史，描述了用于工程化α1-AT，感兴趣的特定突变体的技术，并提供了迄今为止已发布的> 200个α1-AT突变体的附加目录。