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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structural basis for the recognition and cleavage of abasic DNA in Neisseria meningitidis
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Structural basis for the recognition and cleavage of abasic DNA in Neisseria meningitidis

机译：脑膜炎奈瑟氏球菌无碱基DNA的识别和切割的结构基础

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摘要

Base excision repair (BER) is a highly conserved DNA repair pathway throughout all kingdoms from bacteria to humans. Whereas several enzymes are required to complete the multistep repair process of damaged bases, apurinic-apyrimidic (AP) endonucleases play an essential role in enabling the repair process by recognizing intermediary abasic sites cleaving the phosphodiester backbone 5' to the abasic site. Despite extensive study, there is no structure of a bacterial AP endonuclease bound to substrate DNA. Furthermore, the structural mechanism for AP-site cleavage is incomplete. Here we report a detailed structural and biochemical study of the AP endonuclease from Neisseria meningitidis that has allowed us to capture structural intermediates providing more complete snapshots of the catalytic mechanism. Our data reveal subtle differences in AP-site recognition and kinetics between the human and bacterial enzymes that may reflect different evolutionary pressures.
机译：碱基切除修复（BER）是从细菌到人类的所有王国中高度保守的DNA修复途径。尽管需要几种酶来完成受损碱基的多步修复过程，但嘌呤-表皮嘧啶（AP）核酸内切酶通过识别将磷酸二酯主链5'切割成无碱基位点的中间无碱基位点，在使修复过程中起着至关重要的作用。尽管进行了广泛的研究，但没有细菌AP内切核酸酶与底物DNA结合的结构。此外，AP位点切割的结构机制不完整。在这里，我们报告了脑膜炎奈瑟氏菌AP核酸内切酶的详细结构和生化研究，这使我们能够捕获结构中间体，从而提供更完整的催化机理快照。我们的数据揭示了人类和细菌酶之间AP位点识别和动力学的细微差异，这可能反映了不同的进化压力。

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    Duo Lu; Jan Silhan; James T. MacDonald; Elisabeth P. Carpenter; Kirsten Jensen; Christoph M. Tang; Geoff S. Baldwin; Paul S. Freemont;

  • 作者单位

    Centre for Structural Biology, Division of Molecular Biosciences and Department of Microbiology, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom;

    Centre for Structural Biology, Division of Molecular Biosciences and Department of Microbiology, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom;

    Centre for Structural Biology, Division of Molecular Biosciences and Department of Microbiology, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom;

    Centre for Structural Biology, Division of Molecular Biosciences and Department of Microbiology, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom Structural Genomics Consortium, University of Oxford, Old Road Campus, Headington, Oxford 0X3 7DQ, United Kingdom;

    Centre for Structural Biology, Division of Molecular Biosciences and Department of Microbiology, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom;

    Centre for Structural Biology, Division of Molecular Biosciences and Department of Microbiology, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom Sir William Dunn School of Pathology, University of Oxford, Oxford, 0X1 3RE, United Kingdom;

    Centre for Structural Biology, Division of Molecular Biosciences and Department of Microbiology, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom;

    Centre for Structural Biology, Division of Molecular Biosciences and Department of Microbiology, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    X-ray crystallography; genome stability; prokaryote;

    机译：X射线晶体学;基因组稳定性原核生物;

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