AN ATTEMPT TO UNIFY THE STRUCTURE OF POLYMERASES
AN ATTEMPT TO UNIFY THE STRUCTURE OF POLYMERASES
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DOI：
10.1093/protein/3.6.461
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发表时间：
1990-05-01
期刊：
影响因子：
--
通讯作者：
ARGOS, P
中科院分区：
文献类型：
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作者：
DELARUE, M;POCH, O;ARGOS, P
随着RNA和DNA依赖性RNA和DNA聚合酶序列的大量可用性，已经有可能描绘出各种聚合酶类型的一些高度保守区域。在这项工作中，发现来自噬菌体SPO2的DNA聚合酶序列与来自大肠杆菌的聚合酶I的Klenow片段的聚合酶结构域同源，已知该片段与来自肺炎葡萄球菌、水生栖热菌和噬菌体T7和T5的聚合酶结构域密切相关。 SPO2聚合酶与其他五个序列的比对大大缩小了这些蛋白质中的保守基序。其中三个基序与另一种DNA聚合酶类型的所有保守基序合理匹配，所述另一种DNA聚合酶类型以人聚合酶α为特征。还可能在单体DNA依赖性RNA聚合酶中发现这三种基序，并且在DNA聚合酶β中发现其中两种基序。和DNA末端转移酶。后两个基序也与最近在84种RNA依赖性聚合酶中发现的四个基序中的两个相匹配。从已知的E. coli pol I中，这些基序可以暗示空间排列。此外，许多生化实验表明这些基序在共同功能（dNTP结合）中的作用也支持这些推论。这种推测性的假设，试图统一聚合酶的结构，至少在本地，如果不是全球性的，在聚合酶折叠，应该提供一个有用的模型，直接诱变实验探针模板和底物的特异性聚合酶。
With the great availability of sequences from RNA- and DNA-dependent RNA and DNA polymerases, it has become possible to delineate a few highly conserved regions for various polymerase types. In this work a DNA polymerase sequence from bacteriophage SPO2 was found to be homologous to the polymerase domain of the Klenow fragment of polymerase I from Escherichia coli, which is known to be closely related to those from Staphylococcus pneumoniae, Thermus aquaticus and bacteriophages T7 and T5. The alignment of the SPO2 polymerase with the other five sequences considerably narrowed the conserved motifs in these proteins. Three of the motifs matched reasonably all the conserved motifs of another DNA polymerase type, characterized by human polymerase .alpha.. It is also possible to find these three motifs in monomeric DNA-dependent RNA polymerases and two of them in DNA polymerase .beta. and DNA terminal transferases. These latter two motifs also matched two of the four motifs recently identified in 84 RNA-dependent polymerases. From the known tertiary architecture of the Klenow fragment of E. coli pol I, a spatial arrangement can be implied for these motifs. In addition, numerous biochemical experiments suggesting a role for the motifs in a common function (dNTP binding) also support these inferences. This speculative hypothesis, attempting to unify polymerase structure at least locally, if not globally, under the pol I fold, should provide a useful model to direct mutagenesis experiments to probe template and substrate specificity in polymerases.