The rational design and construction of a cuboidal iron-sulfur protein
The rational design and construction of a cuboidal iron-sulfur protein
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DOI：
10.1073/pnas.94.13.6635
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发表时间：
1997-06-24
影响因子：
11.1
通讯作者：
Caradonna, JP
中科院分区：
文献类型：
--
作者：
Coldren, CD;Hellinga, HW;Caradonna, JP
理性蛋白质设计是一种新兴的方法，通过创造新的结构和功能来测试蛋白质化学的一般理论。在这里，我们首次通过合理设计成功地将[Fe4S4]立方簇引入大肠杆菌硫氧还蛋白的疏水核心，硫氧还蛋白是一种通常缺乏金属中心的蛋白质。立方体[Fe4S4]是自组装铁硫团簇的一种稳定形式，被认为代表了一些最早进化的生物氧化还原中心，[Fe4S4]团簇已被用于多种蛋白质，其功能对许多主要生化过程至关重要，从简单的可溶性电子转移剂到电子转移链的膜结合组分，再到复杂金属酶（如氮酶）中的电子储存器。通过将[Fe4S4]簇置于先前未被进化适应的蛋白质环境中，我们可以探索蛋白质基质调节其活性的因素。
Rational protein design is an emerging approach for testing general theories of protein chemistry through the creation of new structures and functions. Here we present the first successful introduction by rational design of a [Fe4S4] cuboidal cluster into the hydrophobic core of Escherichia coli thioredoxin, a protein normally devoid of metal centers. Cuboidal [Fe4S4] is one of the stable forms of self-assembled iron-sulfur clusters that are thought to represent some of the earliest evolved biological redox centers, [Fe4S4] clusters have been recruited for use in a variety of proteins whose functions are central to many of the major biochemical processes ranging from simple soluble electron-transfer agents, to membrane-bound components of electron-transfer chains, to electron reservoirs in complex metalloenzymes such as nitrogenase, By situating an [Fe4S4] cluster into a protein environment not previously adapted by evolution we can explore the factors by which their activity is modulated by the protein matrix.