基于蛋白质骨架的人工水解酶的理性设计

赵媛; 曾金; 林英武

doi:10.7536/PC150232

化学进展 ›› 2015, Vol. 27 ›› Issue (8) :1102-1109 DOI: 10.7536/PC150232

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基于蛋白质骨架的人工水解酶的理性设计

^1,2

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Rational Design of Artificial Hydrolases in Protein Scaffolds

Zhao Yuan¹, Zeng Jin¹, Lin Yingwu*^1,2

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摘要

蛋白质是生命体的重要组成部分,其中生物酶在生命体系中发挥至关重要的作用。蛋白质分子设计是研究生物酶结构与功能关系的重要手段。本文综述了基于蛋白质骨架的人工水解酶的理性设计与功能研究进展,包括对天然蛋白的重新利用和重新改造,基于3-股螺旋、4-股螺旋或锌指蛋白的分子设计,以及血红蛋白(如细胞色素b₅和肌红蛋白突变体)水解酶催化活性的调控等,阐明了人工水解酶分子设计的基本思路与研究方法,为合理构建人工水解酶或其他生物酶提供了重要的信息。人工水解酶的理性设计进展,不但深化我们对天然酶结构-性质-反应-功能关系的认识,而且还提升我们创造具有优越功能的人工生物酶的能力。

Abstract

Proteins are an important part of life, of which enzymes perform vital roles in biological systems. Rational protein design is a key approach for investigating the structure and function relationship of enzymes. This review summarizes the progresses in rational design and functional study of artificial hydrolases in protein scaffolds, including reuse of natural proteins, reconstruction of natural proteins, molecular design based on 3-α-helix, 4-α-helix or zinc-finger proteins, and fine-tuning the hydrolysis activity of heme proteins such as cytochrome b₅ and myoglobin mutants. It illustrates the basic idea and approaches of artificial hydrolase design, which provides valuable clues for rational construction of artificial hydrolase or other enzymes. The progress in rational design of artificial hydrolases not only enriches our understanding of the structure-property-reactivity-function relationship of native enzymes, but also enhances our ability to construct artificial enzymes with advanced functions.

Contents
1 Introduction
2 Mechanisms of hydrolases
3 Hydrolases containing no metal ions
3.1 Reuse of natural proteins
3.2 Reconstruction of natural proteins
4 Hydrolases containing metal ions
4.1 Molecular design based on 3-α-helix
4.2 Molecular design based on 4-α-helix
4.3 Molecular design based on zinc-finger protein
5 Hydrolases containing metal complex
5.1 Explore hydrolysis activity of heme proteins
5.2 Tune hydrolysis activity of heme proteins
6 Conclusion and outlook

Graphical abstract

关键词

蛋白质设计 / 水解酶 / 活性位点 / 生物催化 / 分子机制

Key words

protein design / hydrolases / active site / biological catalysis / mechanism

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赵媛, 曾金, 林英武. 基于蛋白质骨架的人工水解酶的理性设计[J]. 化学进展, 2015, 27(8): 1102-1109 DOI:10.7536/PC150232

Zhao Yuan, Zeng Jin, Lin Yingwu. Rational Design of Artificial Hydrolases in Protein Scaffolds[J]. Progress in Chemistry, 2015, 27(8): 1102-1109 DOI:10.7536/PC150232

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