Towards a comprehensive structural coverage of completed genomes: a structural genomics viewpoint
Towards a comprehensive structural coverage of completed genomes: a structural genomics viewpoint
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DOI：
10.1186/1471-2105-8-86
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发表时间：
2007-03-09
影响因子：
3
通讯作者：
Orengo, Christine A.
中科院分区：
文献类型：
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作者：
Marsden, Russell L.;Lewis, Tony A.;Orengo, Christine A.
背景：结构基因组学计划的建立旨在大规模解析蛋白质结构。对于许多计划，比如蛋白质结构计划（PSI），靶点选择的主要目的侧重于对到目前为止缺乏结构代表的蛋白质家族进行结构表征。因此，深入了解这些家族的数量和分布，以及为实现对所有蛋白质家族的全面结构覆盖可能需要付出哪些努力，是非常有意义的。
结果：在本次分析中，我们使用CATH、Pfam - A和Newfam结构域家族对基因组进行了全面的结构域注释。我们考虑了高通量结构基因组学流程（特别是那些针对包含多个原核同源物的家族的流程）能够获取多大比例的结构未表征家族。在测量基因组的结构域覆盖度时，我们展示了从结构未表征的结构域家族中选择靶点的益处，同时，从大型的结构已表征的蛋白质超家族中选取额外靶点也有好处。
结论：这项工作表明，如果结构基因组学要实现对基因组的全面结构覆盖，从而更深入地了解蛋白质进化的结构和机制，那么这种靶点选择的综合方法是必不可少的。
Background: Structural genomics initiatives were established with the aim of solving protein structures on a large-scale. For many initiatives, such as the Protein Structure Initiative ( PSI), the primary aim of target selection is focussed towards structurally characterising protein families which, so far, lack a structural representative. It is therefore of considerable interest to gain insights into the number and distribution of these families, and what efforts may be required to achieve a comprehensive structural coverage across all protein families.Results: In this analysis we have derived a comprehensive domain annotation of the genomes using CATH, Pfam-A and Newfam domain families. We consider what proportions of structurally uncharacterised families are accessible to high-throughput structural genomics pipelines, specifically those targeting families containing multiple prokaryotic orthologues. In measuring the domain coverage of the genomes, we show the benefits of selecting targets from both structurally uncharacterised domain families, whilst in addition, pursuing additional targets from large structurally characterised protein superfamilies.Conclusion: This work suggests that such a combined approach to target selection is essential if structural genomics is to achieve a comprehensive structural coverage of the genomes, leading to greater insights into structure and the mechanisms that underlie protein evolution.