Identification of a new family of putative PD-(D/E)XK nucleases with unusual phylogenomic distribution and a new type of the active site.
Identification of a new family of putative PD-(D/E)XK nucleases with unusual phylogenomic distribution and a new type of the active site.
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DOI：
10.1186/1471-2164-6-21
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发表时间：
2005-02-18
期刊：
影响因子：
4.4
通讯作者：
Bujnicki JM
中科院分区：
文献类型：
--
作者：
Feder M;Bujnicki JM
通过鉴定未表征蛋白质家族与已表征蛋白质家族和已知结构的进化联系来预测未表征蛋白质家族的结构和功能是基因组学的基石之一。三维折叠的理论分配和蛋白质功能的预测，即使在一个非常普遍的水平，可以促进实验确定的分子作用机制和作用，一个给定的蛋白质家族的成员在细胞中履行。在这里，我们预测的三维折叠和研究的一个大家庭的成员的未表征的蛋白质分类在集群的Orthopathy组数据库为COG 4636的基因组分布。使用蛋白质折叠识别，我们发现COG 4636的成员与来自PD-（D/E）XK超家族的Holliday连接解离酶和其他核酸酶有远程相关。结构建模和序列分析表明，大多数成员的COG 4636表现出一个新的，不寻常的变体的推定的活性位点，其中催化的赖氨酸残基迁移的序列，但保留类似的空间位置相对于其他功能上重要的残基。序列分析表明，COG 4636及其同源物主要存在于蓝细菌中，但也存在于其他细菌门中。它们在定殖的基因组中进行水平转移和广泛增殖;例如在Gloeulopsis violaceus PCC 7421中，它们包含超过2%的所有蛋白质编码基因。因此，COG 4636的成员似乎是一种新型的自私遗传元件，它可能在蓝藻及其入侵的其他物种的基因组动态中发挥重要作用。我们的分析提供了一个平台，实验测定的分子和细胞功能的成员，这个大的蛋白质家族。在提交该手稿之后，在蛋白质数据库（Protein Data Bank）中发布了COG 4636成员之一的晶体结构（代码1 wdj; Idaka，M.，Wada，T.，Murayama，K.，寺田，T.，Kuramitsu，S.，Shirouzu，M.，Yokoyama，S.：来自嗜热栖热菌Hb 8的Tt 1808的晶体结构，待公布）。我们对Tt 1808结构的分析表明，我们正确地预测了COG 4636家族的所有功能上重要的特征，包括PD-（D/E）xK超家族核酸酶的成员资格、三维折叠、推定的催化残基和活性位点的不寻常构型。
Prediction of structure and function for uncharacterized protein families by identification of evolutionary links to characterized families and known structures is one of the cornerstones of genomics. Theoretical assignment of three-dimensional folds and prediction of protein function even at a very general level can facilitate the experimental determination of the molecular mechanism of action and the role that members of a given protein family fulfill in the cell. Here, we predict the three-dimensional fold and study the phylogenomic distribution of members of a large family of uncharacterized proteins classified in the Clusters of Orthologous Groups database as COG4636. Using protein fold-recognition we found that members of COG4636 are remotely related to Holliday junction resolvases and other nucleases from the PD-(D/E)XK superfamily. Structure modeling and sequence analyses suggest that most members of COG4636 exhibit a new, unusual variant of the putative active site, in which the catalytic Lys residue migrated in the sequence, but retained similar spatial position with respect to other functionally important residues. Sequence analyses revealed that members of COG4636 and their homologs are found mainly in Cyanobacteria, but also in other bacterial phyla. They undergo horizontal transfer and extensive proliferation in the colonized genomes; for instance in Gloeobacter violaceus PCC 7421 they comprise over 2% of all protein-encoding genes. Thus, members of COG4636 appear to be a new type of selfish genetic elements, which may fulfill an important role in the genome dynamics of Cyanobacteria and other species they invaded. Our analyses provide a platform for experimental determination of the molecular and cellular function of members of this large protein family. After submission of this manuscript, a crystal structure of one of the COG4636 members was released in the Protein Data Bank (code 1wdj; Idaka, M., Wada, T., Murayama, K., Terada, T., Kuramitsu, S., Shirouzu, M., Yokoyama, S.: Crystal structure of Tt1808 from Thermus thermophilus Hb8, to be published). Our analysis of the Tt1808 structure reveals that we correctly predicted all functionally important features of the COG4636 family, including the membership in the PD-(D/E)xK superfamily of nucleases, the three-dimensional fold, the putative catalytic residues, and the unusual configuration of the active site.
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DOI：
10.1093/bioinformatics/8.3.275
发表时间：
1992-06-01
期刊：
COMPUTER APPLICATIONS IN THE BIOSCIENCES
影响因子：
--
作者：
JONES, DT;TAYLOR, WR;THORNTON, JM
通讯作者：
THORNTON, JM
DOI：
10.1038/79032
发表时间：
2000-09-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Deibert, M;Grazulis, S;Huber, R
通讯作者：
Huber, R
影响因子：
14.9
作者：
Daiyasu, H;Komori, K;Toh, H
通讯作者：
Toh, H
影响因子：
3.5
作者：
Chinen, A;Uchiyama, I;Kobayashi, I
通讯作者：
Kobayashi, I
影响因子：
16
作者：
Hickman, AB;Li, Y;Dyda, F
通讯作者：
Dyda, F