Modulating Mobility: a Paradigm for Protein Engineering?
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- 作者：Margaret McAuley ; David J. Timson
- 关键词：Enzyme engineering ; Molecular dynamics ; Protein flexibility ; Active site ; Biocatalysis ; Conformational change
- 刊名：Applied Biochemistry and Biotechnology
- 出版年：2017
- 出版时间：January 2017
- 年：2017
- 卷：181
- 期：1
- 页码：83-90
- 全文大小：
- 刊物类别：Chemistry and Materials Science
- 刊物主题：Biotechnology; Biochemistry, general;
- 出版者：Springer US
- ISSN：1559-0291
- 卷排序：181
文摘
Proteins are highly mobile structures. In addition to gross conformational changes occurring on, for example, ligand binding, they are also subject to constant thermal motion. The mobility of a protein varies through its structure and can be modulated by ligand binding and other events. It is becoming increasingly clear that this mobility plays an important role in key functions of proteins including catalysis, allostery, cooperativity, and regulation. Thus, in addition to an optimum structure, proteins most likely also require an optimal dynamic state. Alteration of this dynamic state through protein engineering will affect protein function. A dramatic example of this is seen in some inherited metabolic diseases where alternation of residues distant from the active site affects the mobility of the protein and impairs function. We postulate that using molecular dynamics simulations, experimental data or a combination of the two, it should be possible to engineer the mobility of active sites. This may be useful in, for example, increasing the promiscuity of enzymes. Thus, a paradigm for protein engineering is suggested in which the mobility of the active site is rationally modified. This might be combined with more “traditional” approaches such as altering functional groups in the active site.