Structural Analysis of Metal Sites in Proteins: Non-heme Iron Sites as a Case Study
Structural Analysis of Metal Sites in Proteins: Non-heme Iron Sites as a Case Study
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DOI：
10.1016/j.jmb.2009.02.052
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发表时间：
2009-05-01
影响因子：
5.6
通讯作者：
Thornton, Janet M.
中科院分区：
文献类型：
--
作者：
Andreini, Claudia;Bertini, Ivano;Thornton, Janet M.
在金属蛋白中，蛋白质环境调节金属性质以实现所需的目标，这可以是蛋白质稳定或功能。因此，在蛋白质结构提供的原子水平上对金属位点的分析可以有益于蛋白质的功能和进化研究。在这项工作中，我们提出了一个结构的生物信息学方法来研究金属蛋白的基础上的金属网站，包括PDB坐标的蛋白质残基形成的第一和第二协调领域的金属结构模板。我们已经将这种方法应用于非血红素铁网站，已在不同的水平进行了分析。位于不同蛋白质结构域的位点的模板已经被比较，表明作为趋同进化的结果，相似的位点可以在不相关的蛋白质中被发现。位于一个大的超家族的蛋白质中的位点的模板进行了比较，显示了蛋白质的不同进化以实现不同功能的可能机制。此外，模板比较已被用来预测的功能，未表征的蛋白质，显示相似性搜索集中在金属网站可以有利地结合典型的全域比较。最后，金属位点的结构模板可能构成数据库中金属蛋白系统分类的基础。(C)2009年由Elsevier Ltd.出版
In metalloproteins, the protein environment modulates metal properties to achieve the required goal, which can be protein stabilization or function. The analysis of metal sites at the atomic level of detail provided by protein structures can thus be of benefit in functional and evolutionary studies of proteins. In this work, we propose a structural bioinformatics approach to the study of metalloproteins based on structural templates of metal sites that include the PDB coordinates of protein residues forming the first and the second coordination sphere of the metal. We have applied this approach to non-heme iron sites, which have been analyzed at various levels. Templates of sites located in different protein domains have been compared, showing that similar sites can be found in unrelated proteins as the result of convergent evolution. Templates of sites located in proteins of a large superfamily have been compared, showing possible mechanisms of divergent evolution of proteins to achieve different functions. Furthermore, template comparisons have been used to predict the function of uncharacterized proteins, showing that similarity searches focused on metal sites can be advantageously combined with typical whole-domain comparisons. Structural templates of metal sites, finally, may constitute the basis for a systematic classification of metalloproteins in databases. (C) 2009 Published by Elsevier Ltd.