CRYSTAL-STRUCTURE OF RAT DNA-POLYMERASE-BETA - EVIDENCE FOR A COMMON POLYMERASE MECHANISM
CRYSTAL-STRUCTURE OF RAT DNA-POLYMERASE-BETA - EVIDENCE FOR A COMMON POLYMERASE MECHANISM
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DOI：
10.1126/science.7516581
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发表时间：
1994-06-24
期刊：
影响因子：
56.9
通讯作者：
KRAUT, J
中科院分区：
文献类型：
--
作者：
SAWAYA, MR;PELLETIER, H;KRAUT, J
大鼠DNA聚合酶β（pol β）的31千道尔顿催化结构域和整个39千道尔顿酶的结构分别在2.3和3.6埃分辨率下测定。31千道尔顿结构域由手指、手掌和拇指亚结构域组成，排列形成DNA结合通道，使人想起大肠杆菌DNA聚合酶I、HIV-1逆转录酶和噬菌体T7 RNA聚合酶的Klenow片段的聚合酶结构域。氨基末端8千道尔顿结构域通过柔性铰链连接到指状亚结构域。在所有聚合酶序列中发现的两个不变的并与催化活性有关的核苷酸在结构相似但拓扑不同的棕榈内具有相同的几何排列，表明聚合酶保持或可能重新进化了共同的核苷酸转移机制。Mn 2+和脱氧腺苷三磷酸在pot β中的位置证实了不变的三磷酸盐在金属离子和脱氧核苷三磷酸结合中的作用。
Structures of the 31-kilodalton catalytic domain of rat DNA polymerase beta (pol beta) and the whole 39-kilodalton enzyme were determined at 2.3 and 3.6 angstrom resolution, respectively. The 31-kilodalton domain is composed of fingers, palm, and thumb subdomains arranged to form a DNA binding channel reminiscent of the polymerase domains of the Klenow fragment of Escherichia coli DNA polymerase I, HIV-1 reverse transcriptase, and bacteriophage T7 RNA polymerase. The amino-terminal 8-kilodalton domain is attached to the fingers subdomain by a flexible hinge. The two invariant aspartates found in all polymerase sequences and implicated in catalytic activity have the same geometric arrangement within structurally similar but topologically distinct palms, indicating that the polymerases have maintained, or possibly re-evolved, a common nucleotidyl transfer mechanism. The location of Mn2+ and deoxyadenosine triphosphate in pot beta confirms the role of the invariant aspartates in metal ion and deoxynucleoside triphosphate binding.