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首页> 外文学位 >A Tale of Cystathionine beta-synthase from Saccharomyces cerevisiae: Biochemical and Structural Analysis of a Pyridoxal 5'-phosphate Dependent Enzyme.
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A Tale of Cystathionine beta-synthase from Saccharomyces cerevisiae: Biochemical and Structural Analysis of a Pyridoxal 5'-phosphate Dependent Enzyme.

机译：来自酿酒酵母的胱硫醚β-合酶的故事：吡咯醛5'-磷酸依赖性酶的生化和结构分析。

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摘要

Cystathionine beta-synthase (CBS) is a pyridoxal 5'-phosphate (PLP) dependent enzyme. It catalyzes the first reaction in the transsulfuration pathway, in which serine and homocysteine are condensed to give cystathionine. CBS from higher organisms such as Homo sapiens (hCBS) and Melanogaster drosophila (dCBS) contains a heme in the N-terminal domain. This novel combination of cofactors has not been seen in any other protein to date. Though the presence of the heme, whose functions in CBS have yet to be elucidated, is biochemically interesting, its absorption spectra overlap with that of the PLP. Therefore its presence greatly hampers mechanistic studies using UV-Visible absorption spectroscopy. CBS from Saccharomyces cerevisiae (yCBS) naturally lacks the heme-containing N-terminal domain, which makes it an ideal model for the spectroscopic studies. All three CBS' have C-terminal regulatory domains, but their regulation mechanisms are different. Crystal structures of hCBS mutants and wild type dCBS have been solved, but the structure of yCBS has yet to emerge. Here I present the cloning, expression, purification, and crystallization of yCBS wild type and mutants, and try to address some of the differences among the three eukaryotic CBS through biochemical and structural analysis. I also present UV-Visible absorption spectroscopic and structural analysis of a putative CBS hydrazine inhibitor -- whose original role was to help facilitating the crystallization of yCBS -- and propose using the yCBS_Catalytic-Core mutant as a model system for rational design of hCBS inhibitors.
机译：胱硫醚β-合酶（CBS）是吡ido醛5'-磷酸（PLP）依赖性酶。它催化转硫途径中的第一反应，其中丝氨酸和高半胱氨酸缩合生成胱硫醚。来自高等生物（如智人（hCBS）和果蝇黑腹果蝇（dCBS））的CBS在N末端域中含有血红素。迄今为止，辅助因子的这种新颖组合在任何其他蛋白质中均未见。尽管在化学上尚不清楚其在CBS中的功能的血红素的存在在生物化学上令人关注，但其吸收光谱与PLP的吸收光谱重叠。因此，它的存在极大地阻碍了使用紫外可见吸收光谱的机械研究。来自酿酒酵母（yCBS）的CBS自然缺乏含血红素的N末端结构域，这使其成为光谱研究的理想模型。这三个CBS都具有C端调控域，但是它们的调控机制是不同的。 hCBS突变体和野生型dCBS的晶体结构已得到解决，但yCBS的结构尚未出现。在这里，我介绍了yCBS野生型和突变体的克隆，表达，纯化和结晶，并尝试通过生化和结构分析解决这三个真核CBS之间的某些差异。我还介绍了推定的CBS肼抑制剂的紫外可见吸收光谱和结构分析-其最初的作用是帮助促进yCBS的结晶-并建议使用yCBS_Catalytic-Core突变体作为合理设计hCBS抑制剂的模型系统。

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  • 作者

    Tu, Yupeng.;

  • 作者单位

    Brandeis University.;

  • 授予单位 Brandeis University.;
  • 学科 Biochemistry.
  • 学位 Ph.D.
  • 年度 2016
  • 页码 196 p.
  • 总页数 196
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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