Divergence of function in the thioredoxin fold suprafamily: Evidence for evolution of peroxiredoxins from a thioredoxin-like ancestor
Divergence of function in the thioredoxin fold suprafamily: Evidence for evolution of peroxiredoxins from a thioredoxin-like ancestor
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DOI：
10.1021/bi048947r
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发表时间：
2004-11-09
期刊：
影响因子：
2.9
通讯作者：
Babbitt, PC
中科院分区：
文献类型：
--
作者：
Copley, SD;Novak, WRP;Babbitt, PC
硫氧还蛋白折叠存在于具有多种功能的蛋白质中。其中包括过氧化氢还蛋白，它能催化过氧化氢和烷基过氧化氢的还原。尽管硫氧还蛋白和过氧化还蛋白共有的共同结构折叠表明它们可能是从共同的祖先进化而来的，但深入检验这一假说一直是困难的，因为这两个超家族中的蛋白质之间的成对序列同一性在统计学上并不显著。使用鸟枪程序，我们发现在某些细菌中，参与细胞色素成熟的还原酶序列连接硫氧还蛋白和过氧化还蛋白序列。对硫氧还蛋白、细胞色素成熟蛋白和过氧化还蛋白的不同基序的分析为这些蛋白之间的进化关系提供了进一步的支持。在保守的基序中有特定的残基，这些残基是个别蛋白质类别的特征，因此很可能参与这些类别的特定功能。我们利用这些信息，结合现有的结构和功能信息，对这些蛋白质的结构-功能关系有了新的了解，并构建了一个模型，说明过氧化还蛋白是从硫氧还蛋白类祖先中出现的。
The thioredoxin fold is found in proteins that serve a wide variety of functions. Among these are peroxiredoxins, which catalyze the reduction of hydrogen peroxide and alkyl peroxides. Although the common structural fold shared by thioredoxins and peroxiredoxins suggests the possibility that they have evolved from a common progenitor, it has been difficult to examine this hypothesis in depth because pairwise sequence identities between proteins in these two superfamilies are statistically insignificant. Using the Shotgun program, we have found that sequences of reductases involved in maturation of cytochromes in certain bacteria bridge the sequences of thioredoxins and peroxiredoxins. Analysis of motifs found in a divergent set of thioredoxins, cytochrome maturation proteins, and peroxiredoxins provides further support for an evolutionary relationship between these proteins. Within the conserved motifs are specific residues that are characteristic of individual protein classes, and therefore are likely to be involved in the specific functions of those classes. We have used this information, in combination with existing structural and functional information, to gain new insight into the structure-function relationships in these proteins and to Construct a model for the emergence of peroxiredoxins from a thioredoxin-like ancestor.