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首页> 外文期刊>RSC Advances >Structural basis for substrate discrimination by E. coli repair enzyme, AlkB
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Structural basis for substrate discrimination by E. coli repair enzyme, AlkB

机译：大肠杆菌修复酶，ALKB的基材鉴别的结构基础

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摘要

E. coli AlkB, a repair enzyme of the dioxygenase family, catalyses the removal of mutagenic methylated nucleotides from the genome. Known for substrate promiscuity, AlkB's catalytic mechanism and conformational changes accompanying substrate binding have been extensively dissected. However, the structural parameters of various substrates governing their recognition by AlkB still remain elusive. In this work, through solution-state vibrational spectra of methylated substrates bound to AlkB in combination with computational analysis, we show that the recognition specificity is dictated by the protonation states of the substrates. Specificity is conferred predominantly through hydrogen bonding and cation-pi interactions. Furthermore, we report on the interaction of AlkB with normal, unmodified nucleotides, wherein the presence of an exocyclic amino group serves as an essential criterion for the initial process of substrate recognition. Taken together, these results provide a rationale for structural determinants of substrate specificity as well as mode of lesion discrimination employed by AlkB.
机译：大肠杆菌Alc1，DiOxygenase系列的修复酶，催化来自基因组的致致苄基状核苷酸的去除。已经广泛地解剖了用于底物滥交，亚烷型的伴随基底结合的催化机制和构象变化。然而，通过ALKB控制其识别的各种基材的结构参数仍然难以实现。在这项工作中，通过与计算分析结合甲基化底物的甲基化底物的溶液状态振动光谱，我们表明识别特异性由基材的质子化状态决定。主要通过氢键和阳离子-PI相互作用主要赋予特异性。此外，我们报告了碱的相互作用与正常，未改性的核苷酸，其中官方氨基的存在作为初始衬底识别过程的基本标准。总之，这些结果为底物特异性的结构决定因素以及ALKB采用的病变鉴别模式提供了基本原理。

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  • 来源
    《RSC Advances》 |2018年第3期|共11页
  • 作者

    Jayanth Namrata; Ogirala Nirmala; Yadav Anil; Puranik Mrinalini;

  • 作者单位

    Tata Inst Fundamental Res Natl Ctr Biol Sci GKVK Campus Bellary Rd Bangalore 560065 Karnataka India;

    Tata Inst Fundamental Res Natl Ctr Biol Sci GKVK Campus Bellary Rd Bangalore 560065 Karnataka India;

    IISER Pune 411008 Maharashtra India;

    Tata Inst Fundamental Res Natl Ctr Biol Sci GKVK Campus Bellary Rd Bangalore 560065 Karnataka India;

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  • 正文语种 eng
  • 中图分类 化学;
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