Structural and Mechanistic Study of Mammalian Thiol Dioxygenases

哺乳动物硫醇双加氧酶的结构和机制研究

基本信息

  • 批准号:
    1808637
  • 负责人:
  • 金额:
    $ 45万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-08-15 至 2022-09-30
  • 项目状态:
    已结题

项目摘要

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Aimin Liu from The University of Texas at San Antonio to investigate the structure and mechanism of two human enzymes involved in the oxidative sulfur metabolism. The two enzymes of interest, cysteine dioxygenase and cysteamine dioxygenase, are responsible for activating oxygen to process organic thiol moieties. The activity of these two enzymes is essential to manage metabolic cysteine and taurine concentrations and it is associated with autoimmune and neurological conditions, cellular signaling, energy balance, and fat metabolism. Integrated training is incorporated in the research project, which provides to students comprehensive and hands-on learning opportunities in biochemical and structural biology techniques. A multimedia presentation on electron paramagnetic resonance spectroscopy will be created and used to provide to students a tangible demonstration of how this advanced spectroscopy can clarify chemical properties of critical biomolecular systems. This research project seeks to reveal the mechanistic implications of adding oxygen atoms to electron-rich sulfur as well as the nature of the catalytic contribution of a protein-derived cofactor. The thiol dioxygenases utilize a mononuclear ferrous center to facilitate the incorporation of molecular oxygen into the thiol moiety of their respective substrates. These enzymes stand out as unique among dioxygenases because they add two of the oxygen atoms of molecular oxygen to a single substrate atom. Though other dioxygenases have been well studied, thiol dioxygenation is expected to proceed via a distinct mechanism that has not been well established yet. Dr. Liu is investigating the formation of the catalytic ensemble of these enzymes, namely an iron- and oxygen-dependent process for generating a catalytic amplifier known as the protein-derived cofactor. A wide array of techniques, including protein engineering, EPR spectroscopy, stopped-flow rapid kinetics, and protein X-ray crystallography, are employed in the determination of the chemical steps of cofactor biogenesis and sulfur oxygenation. The completion of this project is expected to reveal new mechanistic implications of adding two oxygen atoms to one electron-rich sulfur as well as the nature of the catalytic contribution of the protein-derived cofactor to sulfur metabolism.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
有了这个奖项,化学部的生命过程化学项目正在资助德克萨斯大学圣安东尼奥分校的刘爱民博士研究参与氧化硫代谢的两种人类酶的结构和机制。感兴趣的两种酶,半胱氨酸双加氧酶和半胱胺双加氧酶,负责活化氧以加工有机硫醇部分。这两种酶的活性对于管理代谢半胱氨酸和牛磺酸浓度是必不可少的,并且它与自身免疫和神经病症、细胞信号传导、能量平衡和脂肪代谢相关。研究计划包括综合训练,为学生提供全面和实践的学习机会,学习生物化学和结构生物学技术。电子顺磁共振光谱学的多媒体演示将被创建并用于为学生提供这种先进的光谱学如何澄清关键生物分子系统的化学性质的有形演示。 该研究项目旨在揭示将氧原子添加到富含电子的硫中的机械含义以及蛋白质衍生辅因子的催化贡献的性质。 硫醇双加氧酶利用单核亚铁中心来促进分子氧掺入其各自底物的硫醇部分中。这些酶在双加氧酶中脱颖而出,因为它们将分子氧的两个氧原子添加到单个底物原子上。虽然其他双加氧酶已经得到很好的研究,硫醇双加氧预计将通过一个独特的机制,尚未得到很好的建立。刘博士正在研究这些酶的催化体系的形成,即一个铁和氧依赖的过程,用于产生一种被称为蛋白质衍生辅因子的催化放大器。一系列广泛的技术,包括蛋白质工程,EPR光谱,停流快速动力学,和蛋白质X射线晶体学,在确定的化学步骤的辅因子生物合成和硫氧化。该项目的完成有望揭示将两个氧原子添加到一个富含电子的硫的新的机理含义,以及蛋白质衍生的辅因子对硫代谢的催化作用的性质。该奖项反映了NSF的法定使命,并通过使用基金会的智力价值和更广泛的影响审查标准进行评估,被认为值得支持。

项目成果

期刊论文数量(12)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cofactor Biogenesis in Cysteamine Dioxygenase: C−F Bond Cleavage with Genetically Incorporated Unnatural Tyrosine
半胱胺双加氧酶中的辅因子生物发生:基因掺入的非天然酪氨酸导致 C–F 键断裂
  • DOI:
    10.1002/ange.201803907
  • 发表时间:
    2018
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Wang, Yifan;Griffith, Wendell P.;Li, Jiasong;Koto, Teruaki;Wherritt, Daniel J.;Fritz, Elizabeth;Liu, Aimin
  • 通讯作者:
    Liu, Aimin
Probing Extradiol Dioxygenase Mechanism in NAD+ Biosynthesis by Viewing Reaction Cycle Intermediates
通过观察反应循环中间体探讨 NAD 生物合成中的外二醇双加氧酶机制
Observing 3-hydroxyanthranilate-3,4-dioxygenase in action through a crystalline lens
通过晶状体观察 3-羟基邻氨基苯甲酸-3,4-双加氧酶的作用
Probing the Cys-Tyr Cofactor Biogenesis in Cysteine Dioxygenase by the Genetic Incorporation of Fluorotyrosine
  • DOI:
    10.1021/acs.biochem.9b00006
  • 发表时间:
    2019-04-30
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Li, Jiasong;Koto, Teruaki;Liu, Aimin
  • 通讯作者:
    Liu, Aimin
Characterization of the non-heme iron center of cysteamine dioxygenase and its interaction with substrates
半胱胺双加氧酶非血红素铁中心的表征及其与底物的相互作用
  • DOI:
    10.1074/jbc.ra120.013915
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    4.8
  • 作者:
    Wang, Yifan;Davis, Ian;Chen, Yan;Naik, Sunil G.;Griffith, Wendell P.;Liu, Aimin
  • 通讯作者:
    Liu, Aimin
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Aimin Liu其他文献

A study on the riprap movement based on marine hydrodynamic model and field observation
基于海洋水动力模型和现场观测的抛石运动研究
  • DOI:
    10.1080/17445302.2022.2129916
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    2.1
  • 作者:
    Zhichao Dong;Bin Li;Haowen Wu;Aimin Liu;Aijun Zhuge;Ziqiang Yin
  • 通讯作者:
    Ziqiang Yin
Photovoltaic characterization of poly(2,5-bis(3-dodecylthiophen-2-yl)-2′,2″-biselenophene) for organic solar cells
有机太阳能电池用聚(2,5-双(3-十二烷基噻吩-2-基)-2′,2″-双硒吩)的光伏表征
  • DOI:
    10.1016/j.solmat.2009.10.025
  • 发表时间:
    2010
  • 期刊:
  • 影响因子:
    0
  • 作者:
    F. Qiao;X. Hou;Yong Lu;Hui Chen;Aimin Liu;Xiao Hu;Ng Siu Choon
  • 通讯作者:
    Ng Siu Choon
Chemical reduction of the diferric/radical center in protein R2 from mouse ribonucleotide reductase is independent of the proposed radical transfer pathway
小鼠核糖核苷酸还原酶对蛋白质 R2 中二铁/自由基中心的化学还原与所提出的自由基转移途径无关
  • DOI:
  • 发表时间:
    2002
  • 期刊:
  • 影响因子:
    0
  • 作者:
    A. Davydov;Maria Öhrström;Aimin Liu;L. Thelander;A. Gräslund
  • 通讯作者:
    A. Gräslund
Effect of Fecal Excretion on Dioxins and Accumulation Controlled in Rat by Koya-tofu and Polydextrose
高野豆腐和聚葡萄糖对大鼠粪便排泄及二恶英蓄积的影响
  • DOI:
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Aimin Liu;M. Nakano;Y. Kushi;H. Kayahara
  • 通讯作者:
    H. Kayahara
New geometric viewpoints to Chen chaotic system
  • DOI:
    10.18514/MMN.2022.3787
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
  • 作者:
    Xiaoting Lu;Yongjian Liu;Aimin Liu;Chunsheng Feng
  • 通讯作者:
    Chunsheng Feng

Aimin Liu的其他文献

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{{ truncateString('Aimin Liu', 18)}}的其他基金

Cys-Tyr Cofactor in Iron and Copper Proteins
铁和铜蛋白质中的半胱氨酸-酪氨酸辅因子
  • 批准号:
    2204225
  • 财政年份:
    2022
  • 资助金额:
    $ 45万
  • 项目类别:
    Standard Grant
Structure-Function Correlations in a Type III Extradiol Dioxygenase
III 型外二醇双加氧酶的结构-功能相关性
  • 批准号:
    1623856
  • 财政年份:
    2016
  • 资助金额:
    $ 45万
  • 项目类别:
    Continuing Grant
Structure-Function Correlations in a Type III Extradiol Dioxygenase
III 型外二醇双加氧酶的结构-功能相关性
  • 批准号:
    1309942
  • 财政年份:
    2013
  • 资助金额:
    $ 45万
  • 项目类别:
    Continuing Grant
Functional Analysis of cilia in Hedgehog signaling and Gli activity regulation
纤毛在 Hedgehog 信号传导和 Gli 活性调节中的功能分析
  • 批准号:
    1257540
  • 财政年份:
    2013
  • 资助金额:
    $ 45万
  • 项目类别:
    Continuing Grant
Functional Analysis of Cilia in Hedgehog Signaling and Gli Activity Regulation
纤毛在 Hedgehog 信号传导和 Gli 活性调节中的功能分析
  • 批准号:
    0949877
  • 财政年份:
    2010
  • 资助金额:
    $ 45万
  • 项目类别:
    Standard Grant
Mechanistic Studies of Tryptophan Oxidizing Enzymes
色氨酸氧化酶的机理研究
  • 批准号:
    0843537
  • 财政年份:
    2009
  • 资助金额:
    $ 45万
  • 项目类别:
    Continuing Grant

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Catalytically inactive Cas9-induced genome destabilization: mechanistic study and applications to manipulation of structural variations
催化失活的 Cas9 诱导的基因组不稳定:结构变异操纵的机制研究和应用
  • 批准号:
    19K22397
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Structural and mechanistic study of C-N bond forming cytochrome P450 enzyme
C-N键形成细胞色素P450酶的结构和机制研究
  • 批准号:
    17H06579
  • 财政年份:
    2017
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Self-organization of hydrophobin membranes formation at flattened-top domical water drops: a structural and mechanistic study using Atomic Force Microscope
平顶圆顶水滴疏水蛋白膜形成的自组织:使用原子力显微镜的结构和机制研究
  • 批准号:
    26600005
  • 财政年份:
    2014
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Cross-regulation of post-translational protein modifications and effects on the histone H3 tail conformations/dynamics: A structural and mechanistic study on whole nucleosomes by Nuclear Magnetic Resonance (NMR) spectroscopy.
翻译后蛋白质修饰的交叉调节以及对组蛋白 H3 尾部构象/动力学的影响:通过核磁共振 (NMR) 光谱对整个核小体进行结构和机制研究。
  • 批准号:
    247285007
  • 财政年份:
    2013
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    $ 45万
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Structural /Mechanistic Study of Lantibiotic Biosynthetic Enzymes & Autoimmunity
羊毛硫抗生素生物合成酶的结构/机理研究
  • 批准号:
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    7769481
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    2006
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Structural /Mechanistic Study of Lantibiotic Biosynthetic Enzymes & Autoimmunity
羊毛硫抗生素生物合成酶的结构/机理研究
  • 批准号:
    7171896
  • 财政年份:
    2006
  • 资助金额:
    $ 45万
  • 项目类别:
Structural /Mechanistic Study of Lantibiotic Biosynthetic Enzymes & Autoimmunity
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  • 批准号:
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STRUCTURAL AND MECHANISTIC STUDY OF SIROHEME SYNTHASE
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