Structural principles for computational and de novo design of 4Fe-4S metalloproteins.
Structural principles for computational and de novo design of 4Fe-4S metalloproteins.
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DOI：
10.1016/j.bbabio.2015.10.001
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发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Noy D
中科院分区：
文献类型：
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作者：
Nanda V;Senn S;Pike DH;Rodriguez-Granillo A;Hansen WA;Khare SD;Noy D
金属蛋白中的铁硫中心可以在广泛的电势范围内获得多种氧化态，使它们能够参与各种电子转移反应并充当高能氧化还原过程的催化剂。固氮酶 FeMoCO 簇通过八电子转移步骤将二氮转化为氨。含有细菌铁氧还蛋白的 2(Fe4S4) 是一种进化上古老的金属蛋白折叠，被认为是现存氧化还原酶的原始祖先。控制由铁硫中心介导的化学转化，例如固氮、制氢以及光合作用中涉及的电子转移反应，对于可持续化学和能源生产计划至关重要。因此，人们对设计铁硫蛋白作为最小模型以获得对复杂自然系统的基本了解以及作为工业和能源应用的先导分子产生了浓厚的兴趣。在这里，我们讨论天然铁硫蛋白的显着结构特征以及它们如何指导设计原则。在这些原则的背景下分析了过去设计的模型结构，提出了增强设计的潜在方向，并提出了铁硫蛋白设计的新领域。
Iron-sulfur centers in metalloproteins can access multiple oxidation states over a broad range of potentials, allowing them to participate in a variety of electron transfer reactions and serving as catalysts for high-energy redox processes. The nitrogenase FeMoCO cluster converts di-nitrogen to ammonia in an eight-electron transfer step. The 2(Fe4S4) containing bacterial ferredoxin is an evolutionarily ancient metalloprotein fold and is thought to be a primordial progenitor of extant oxidoreductases. Controlling chemical transformations mediated by iron-sulfur centers such as nitrogen fixation, hydrogen production as well as electron transfer reactions involved in photosynthesis are of tremendous importance for sustainable chemistry and energy production initiatives. As such, there is significant interest in the design of iron-sulfur proteins as minimal models to gain fundamental understanding of complex natural systems and as lead-molecules for industrial and energy applications. Herein, we discuss salient structural characteristics of natural iron-sulfur proteins and how they guide principles for design. Model structures of past designs are analyzed in the context of these principles and potential directions for enhanced designs are presented, and new areas of iron-sulfur protein design are proposed.