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首页> 外文学位 >Expression and functional characterization of monoamine oxidase from the zebrafish (Danio rerio): Comparisons with human monoamine oxidases A and B.
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Expression and functional characterization of monoamine oxidase from the zebrafish (Danio rerio): Comparisons with human monoamine oxidases A and B.

机译：斑马鱼（Danio rerio）单胺氧化酶的表达和功能表征：与人单胺氧化酶A和B的比较。

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摘要

Monoamine Oxidases (MAO) are flavin containing enzymes located in the outer mitochondrial membrane. Mammals, including humans are shown to contain two forms of this enzyme as MAO A and MAO B. However, not all organisms contain two separate genes expressing these enzymes. Recent studies have shown that zebrafish, a popular teleost organism suitable for various pharmacological applications, contains a single MAO gene. It was proposed that human and teleost MAOs are co-orthologs and share a single common ancestor that underwent a gene duplication event. In addition, studies with whole zebrafish neural tissues have shown that zebrafish MAO exhibit properties closer to human MAO A. To test this hypothesis and to provide the first detailed characterization of zebrafish MAO (zMAO), we developed a high-level expression and purification system for zMAO where we could obtain 235 mg of protein from 0.5 L culture of Pichia pastoris. Then we performed the first detailed functional analysis of the protein with various MAO A and MAO B specific substrates and inhibitors. Here, we also present a comprehensive analysis of quantitive structure relationship of zMAO catalysis in comparison with the human MAO isoforms. Overall data suggest that zMAO contains the properties of both human MAO A and MAO B with properties closer to those of MAO A. The studies from this dissertation provide extensive analysis of this single form of the enzyme and are aimed to be helpful in the pharmacological studies that target designing better drugs targeting MAO using this zebrafish as a system.
机译：单胺氧化酶（MAO）是位于线粒体外膜的含有黄素的酶。哺乳动物（包括人类）被证明含有两种形式的这种酶，如MAO A和MAOB。但是，并非所有生物都包含两种表达这些酶的独立基因。最近的研究表明，斑马鱼是一种适合各种药理应用的流行硬骨鱼生物，包含单个MAO基因。有人提出，人类和硬骨的MAO是同系同源物，并且共享经历基因复制事件的单个共同祖先。此外，对整个斑马鱼神经组织的研究表明，斑马鱼MAO的特性更接近于人类MAOA。为验证这一假设并提供斑马鱼MAO（zMAO）的第一个详细特征，我们开发了一种高级表达和纯化系统对于zMAO，我们可以从0.5 L巴斯德毕赤酵母培养物中获得235 mg蛋白质。然后，我们使用各种MAO A和MAO B特异性底物和抑制剂对蛋白质进行了首次详细的功能分析。在这里，我们还提出了与人类MAO同工型相比zMAO催化的定量结构关系的全面分析。总体数据表明，zMAO包含人MAO A和MAO B的性质，其性质更接近于MAO A的性质。本论文的研究为这种单一形式的酶提供了广泛的分析，旨在为药理研究提供帮助该目标使用该斑马鱼作为系统设计针对MAO的更好药物。

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  • 作者

    Kacar, Betul.;

  • 作者单位

    Emory University.;

  • 授予单位 Emory University.;
  • 学科 Chemistry Biochemistry.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 203 p.
  • 总页数 203
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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