Human DNA polymerase α: predicted functional domains and relationships with viral DNA polymerases
Human DNA polymerase α: predicted functional domains and relationships with viral DNA polymerases
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DOI：
10.1096/fasebj.3.1.2642867
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发表时间：
1989-01
期刊：
影响因子：
--
通讯作者：
T. Wang;S. Wong;D. Korn
中科院分区：
文献类型：
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作者：
T. Wang;S. Wong;D. Korn
从全长cDNA推导的人DNA聚合酶α的一级序列包含与来自大肠杆菌Escherichia coli PRD 1和T4、芽孢杆菌噬菌体Escherichia 19、酵母DNA聚合酶I、酵母线性质粒pGKL 1、玉米S1线粒体DNA、疱疹家族病毒、牛痘病毒和腺病毒的复制型DNA聚合酶序列惊人相似的区域。这些同源区域在这个广阔的系统发育范围内的保守性表明，这些原核和真核DNA聚合酶可能都是从一个共同的原始基因进化而来的。基于酵母和单纯疱疹病毒研究的序列分析和遗传结果，这些共识序列被建议定义潜在的网站，subserve在DNA聚合酶反应中的重要作用。这些保守区域中的两个似乎直接参与底物脱氧核苷酸相互作用所需的活性位点。朝向羧基末端的一个区域有可能成为DNA相互作用结构域，而预测潜在的DNA引发酶相互作用结构域朝向氨基末端。这些结构域的临时分配可用于鉴定具有致病意义的病毒DNA聚合酶中功能同源催化位点的独特或不同特征，从而用于指导更合理的抗病毒药物设计。Wang，T. S. -E.黄，S. W的; Korn，D.人类DNA聚合酶α：预测的功能域和与病毒DNA聚合酶的关系。FASEB J. 3：14 - 21; 1989.
The primary sequence of human DNA polymerase α deduced from the full‐length cDNA contains regions of striking similarity to sequences in replicative DNA polymerases from Escherichia coli phages PRD1 and T4, Bacillus phage ɸ19, yeast DNA polymerase I, yeast linear plasmid pGKL1, maize S1 mitochondrial DNA, herpes family viruses, vaccinia virus, and adenovirus. The conservation of these homologous regions across this vast phylogenetic expanse indicates that these prokaryotic and eukaryotic DNA polymerases may all have evolved from a common primordial gene. Based on the sequence analysis and genetic results from yeast and herpes simplex virus studies, these consensus sequences are suggested to define potential sites that subserve essential roles in the DNA polymerase reaction. Two of these conserved regions appear to participate directly in the active site required for substrate deoxynucleotide interaction. One region toward the carboxyl‐terminus has the potential to be the DNA interacting domain, whereas a potential DNA primase interaction domain is predicted toward the amino‐terminus. The provisional assignment of these domains can be used to identify unique or dissimilar features of functionally homologous catalytic sites in viral DNA polymerases of pathogenetic significance and thereby serve to guide more rational antiviral drug design.— Wang, T. S.‐E.; Wong, S. W.; Korn, D. Human DNA polymerase α: predicted functional domains and relationships with viral DNA polymerases. FASEB J. 3: 14‐21; 1989.