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首页> 外文期刊>Acta crystallographica.Section D. Biological crystallography >Structure of a double-stranded DNA (6-4) photoproduct in complex with the 64M-5 antibody Fab
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Structure of a double-stranded DNA (6-4) photoproduct in complex with the 64M-5 antibody Fab

机译:双链DNA的结构(6 - 4)photoproduct在复杂与64年m-5抗体工厂

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DNA photoproducts with (6-4) pyrimidine-pyrimidone adducts formed by ultraviolet radiation have been implicated in mutagenesis and cancer. The crystal structure of double-stranded DNA containing the (6-4) photoproduct in complex with the anti-(6-4)-photoproduct antibody 64M-5 Fab was determined at 2.5? resolution. The T(6-4)T segment and the 5′-side adjacent adenosine are flipped out of the duplex and are accommodated in the concave antigen-binding pocket composed of six complementarity-determining regions (CDRs). A loop comprised of CDR L1 residues is inserted between the flipped-out T(6-4)T segment and the complementary DNA. The separation of strands by the insertion of the loop facilitates extensive and specific recognition of the photoproduct. The DNA helices flanking the T(6-4)T segment are kinked by 87°. The 64M-5 Fab recognizes the T(6-4)T segment dissociated from the complementary strand, indicating that the (6-4) photoproduct can be detected in double-stranded DNA as well as in single-stranded DNA using the 64M-5 antibody. The structure and recognition mode of the 64M-5 antibody were compared with those of the DNA (6-4) photolyase and nucleotide-excision repair protein DDB1-DDB2. These proteins have distinctive binding-site structures that are appropriate for their functions, and the flipping out of the photolesion and the kinking of the DNA are common to mutagenic (6-4) photoproducts recognized by proteins.
机译:DNA photoproducts pyrimidine-pyrimidone (6 - 4)加合物形成的紫外线辐射涉及诱变和癌症。双链DNA包含结构(6 - 4) photoproduct与复杂(反)- 6 - 4 -photoproduct抗体64 m-5工厂确定在2.5吗?段和5 '端相邻腺苷翻出双工,适应凹antigen-binding口袋组成的complementarity-determining六个区域(CDRs)。循环组成的CDR L1残留物被插入之间的乐歪了T(6 - 4)和T段互补的DNA。插入的循环促进广泛photoproduct的和特定的识别。DNA螺旋侧翼T T段(6 - 4)弯折的87°。T(6 - 4)段的分离互补链,这表明(6 - 4)在双链photoproduct能被探测到DNA单链DNA以及使用64年m-5抗体。模式的64 m-5抗体进行比较(6 - 4)光裂合酶和DNA核苷酸切除修复蛋白质DDB1-DDB2。这些蛋白质有独特的结合位点结构是适合他们的功能,烙的photolesion扭结的DNA是常见的诱变(6 - 4)photoproducts认可蛋白质。

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