De novo metalloprotein design.
De novo metalloprotein design.
复制标题
DOI：
10.1038/s41570-021-00339-5
复制
发表时间：
2022-01
影响因子：
36.3
通讯作者：
DeGrado, William F.
中科院分区：
文献类型：
--
作者：
Chalkley, Matthew J.;Mann, Samuel I.;DeGrado, William F.
天然金属蛋白具有多种功能--从传感到电子传递和催化--其中每个配体和金属的位置和性质由蛋白质结构决定。从头蛋白质设计的目的是定义一个编码特定结构和功能的氨基酸序列，为(金属)蛋白质的假设内部工作提供关键测试。到目前为止，从头开始的金属蛋白使用简单、对称的三级结构--没有被天然蛋白质的大尺寸和进化标记所复杂--来询问结构功能假说。在这篇综述中，我们讨论了从头开始设计的应用，例如诱导复杂的、越来越不对称的配体几何来实现功能的蛋白质，以及使用更规范的配体几何来实现稳定性。从头设计已被用来探索蛋白质如何微调氧化还原电位，并催化氧化和水解反应。随着对结构-功能关系的深入了解，功能蛋白已经被创造出来，包括O2依赖的氧化酶、快速水解酶和多质子/多电子还原酶。此外，蛋白质现在可以使用来自无机化学的外来生物金属或辅因子和原理来设计，以获得新的自然功能。这些结果和计算蛋白质设计方面的进展表明，各种功能金属蛋白的从头设计具有光明的前景。这篇综述描述了金属蛋白的从头设计，它执行着许多生命所必需的功能。通过了解蛋白质结构的对称性和金属活性中心之间的关系，我们可以从头开始设计新型的、具有功能的金属蛋白。
Natural metalloproteins perform many functions — ranging from sensing to electron transfer and catalysis — in which the position and property of each ligand and metal, is dictated by protein structure. De novo protein design aims to define an amino acid sequence that encodes a specific structure and function, providing a critical test of the hypothetical inner workings of (metallo)proteins. To date, de novo metalloproteins have used simple, symmetric tertiary structures — uncomplicated by the large size and evolutionary marks of natural proteins — to interrogate structure-function hypotheses. In this Review, we discuss de novo design applications, such as proteins that induce complex, increasingly asymmetric ligand geometries to achieve function, as well as the use of more canonical ligand geometries to achieve stability. De novo design has been used to explore how proteins fine-tune redox potentials and catalyse both oxidative and hydrolytic reactions. With an increased understanding of structure-function relationships, functional proteins including O2-dependent oxidases, fast hydrolases, and multi-proton/multi-electron reductases, have been created. In addition, proteins can now be designed using xeno-biological metals or cofactors and principles from inorganic chemistry to derive new-to-nature functions. These results and the advances in computational protein design suggest a bright future for the de novo design of diverse, functional metalloproteins. This Review describes the de novo design of metalloproteins, which perform numerous functions essential to life. By understanding, the relationship between the symmetry of the protein structure and the metal active site, we can design novel, functional metalloproteins from scratch.
登录
查看更多内容
影响因子：
15
作者：
Berwick MR;Lewis DJ;Jones AW;Parslow RA;Dafforn TR;Cooper HJ;Wilkie J;Pikramenou Z;Britton MM;Peacock AF
通讯作者：
Peacock AF
影响因子：
8.4
作者：
Anderson JLR;Armstrong CT;Kodali G;Lichtenstein BR;Watkins DW;Mancini JA;Boyle AL;Farid TA;Crump MP;Moser CC;Dutton PL
通讯作者：
Dutton PL
影响因子：
5.6
作者：
Calhoun, JR;Kono, H;Saven, JG
通讯作者：
Saven, JG
影响因子：
5.6
作者：
BARLOW, DJ;THORNTON, JM
通讯作者：
THORNTON, JM
切换金属环境的手性会改变设计肽中的配位模式。
影响因子：
16.6
作者：
Peacock, Anna F. A.;Stuckey, Jeanne A.;Pecoraro, Vincent L.
通讯作者：
Pecoraro, Vincent L.