Testing novel hypotheses in Mtu RecA intein splicing

测试 Mtu RecA 内含肽剪接的新假设

基本信息

  • 批准号:
    7299036
  • 负责人:
  • 金额:
    $ 29.44万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2007
  • 资助国家:
    美国
  • 起止时间:
    2007-09-01 至 2012-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Protein splicing is a precise post-translational process in which an intervening protein sequence, intein, is removed from a precursor protein with the concomitant ligation of the flanking sequences, N- and C-exteins. Although the basic steps of protein splicing are well-known, the catalytic mechanisms of intein splicing are still poorly understood. Advancing our fundamental knowledge of protein splicing can have two major impacts: Inteins have found extensive applications in protein engineering and biotechnology and therefore are an indispensable tool for biomedical research and potentially for therapies of diseases. Because only unicellular organisms have inteins vital for their survival, intein inhibitors can develop into a new class of antimicrobial drug with little toxicity for human cells, especially for Mycobacterium tuberculosis (Mtu). We propose two new mechanistic hypotheses for conserved residues H73 and D422 in Mtu RecA intein. These two hypotheses have been supported by diverse experimental evidence from genetics, in vivo splicing data in intein mutants, solution NMR studies and by calculations. Our specific aims are to test these two hypotheses using a combination of NMR structural biology methods, biochemical characterization of splicing reaction and molecular dynamics simulation to prove or refute these two novel hypotheses. In the process, new methods and concepts for protein splicing will be generated. The results from our research will greatly enhance our understanding the mechanisms of protein splicing and contribute to the application of inteins in biotechnology and potentially in treating diseases. The long term goal is to delineate the complete catalytic mechanisms of protein splicing by applying solution NMR in an interdisciplinary approach for studying enzyme catalysis, structure, dynamics and function.
描述(由申请人提供):蛋白质剪接是一种精确的翻译后过程,其中从前体蛋白质中去除间插蛋白质序列内含肽,同时连接侧翼序列N-和C-外显肽。虽然蛋白质剪接的基本步骤是众所周知的,内含肽剪接的催化机制仍然知之甚少。推进我们对蛋白质剪接的基础知识可以产生两个主要影响:内含肽在蛋白质工程和生物技术中有广泛的应用,因此是生物医学研究和潜在疾病治疗不可或缺的工具。 由于只有单细胞生物具有对其生存至关重要的内含肽,内含肽抑制剂可以发展成为一类对人类细胞,特别是对结核分枝杆菌(Mtu)毒性很小的新型抗菌药物。我们提出了两个新的机制的假设Mtu RecA内含肽中的保守残基H73和D422。这两个假说已经得到了来自遗传学、内含肽突变体体内剪接数据、溶液NMR研究和计算的各种实验证据的支持。我们的具体目标是测试这两个假设,结合使用NMR结构生物学方法,剪接反应的生化表征和分子动力学模拟,以证明或反驳这两个新的假设。在此过程中,将产生新的蛋白质剪接方法和概念。我们的研究结果将大大提高我们对蛋白质剪接机制的理解,并有助于内含肽在生物技术中的应用,并可能在治疗疾病。长期目标是通过应用溶液NMR以跨学科的方法研究酶催化,结构,动力学和功能来描绘蛋白质剪接的完整催化机制。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Chunyu Wang其他文献

Chunyu Wang的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Chunyu Wang', 18)}}的其他基金

Predoctoral Training Program for Alzheimer’s Disease at the Interface of Data Science, Engineering and Biology
数据科学、工程和生物学交叉领域的阿尔茨海默病博士前培训项目
  • 批准号:
    10628106
  • 财政年份:
    2023
  • 资助金额:
    $ 29.44万
  • 项目类别:
The Alzheimer's Disease Clinical and Translational Research (ADCTR) Training Program
阿尔茨海默病临床和转化研究 (ADCTR) 培训计划
  • 批准号:
    10221565
  • 财政年份:
    2017
  • 资助金额:
    $ 29.44万
  • 项目类别:
Development of data science course and summer bootcamp for ADRD researchers
为 ADRD 研究人员开发数据科学课程和夏季训练营
  • 批准号:
    10405365
  • 财政年份:
    2017
  • 资助金额:
    $ 29.44万
  • 项目类别:
The Alzheimer's Disease Clinical and Translational Research (ADCTR) Training Program
阿尔茨海默病临床和转化研究 (ADCTR) 培训计划
  • 批准号:
    9977904
  • 财政年份:
    2017
  • 资助金额:
    $ 29.44万
  • 项目类别:
Testing novel hypotheses in Mtu RecA intein splicing
测试 Mtu RecA 内含肽剪接的新假设
  • 批准号:
    8000230
  • 财政年份:
    2010
  • 资助金额:
    $ 29.44万
  • 项目类别:
Testing novel hypotheses in Mtu RecA intein splicing
测试 Mtu RecA 内含肽剪接的新假设
  • 批准号:
    7911738
  • 财政年份:
    2007
  • 资助金额:
    $ 29.44万
  • 项目类别:
Testing novel hypotheses in Mtu RecA intein splicing
测试 Mtu RecA 内含肽剪接的新假设
  • 批准号:
    7483631
  • 财政年份:
    2007
  • 资助金额:
    $ 29.44万
  • 项目类别:
Testing novel hypotheses in Mtu RecA intein splicing
测试 Mtu RecA 内含肽剪接的新假设
  • 批准号:
    7680970
  • 财政年份:
    2007
  • 资助金额:
    $ 29.44万
  • 项目类别:
Testing novel hypotheses in Mtu RecA intein splicing
测试 Mtu RecA 内含肽剪接的新假设
  • 批准号:
    7681489
  • 财政年份:
    2007
  • 资助金额:
    $ 29.44万
  • 项目类别:
Testing novel hypotheses in Mtu RecA intein splicing
测试 Mtu RecA 内含肽剪接的新假设
  • 批准号:
    8137429
  • 财政年份:
    2007
  • 资助金额:
    $ 29.44万
  • 项目类别:

相似海外基金

Collaborative Research: NSF-DFG: CAS: Electrochemical Hydrogenation of Amides and Esters
合作研究:NSF-DFG:CAS:酰胺和酯的电化学氢化
  • 批准号:
    2140205
  • 财政年份:
    2022
  • 资助金额:
    $ 29.44万
  • 项目类别:
    Standard Grant
Collaborative Research: NSF-DFG: CAS: Electrochemical Hydrogenation of Amides and Esters
合作研究:NSF-DFG:CAS:酰胺和酯的电化学氢化
  • 批准号:
    2140196
  • 财政年份:
    2022
  • 资助金额:
    $ 29.44万
  • 项目类别:
    Standard Grant
Atroposelective Synthesis of Hindered Amides - Exploration of Synthetic Peptide Catalysts -
受阻酰胺的天体选择性合成-合成肽催化剂的探索-
  • 批准号:
    504378162
  • 财政年份:
    2022
  • 资助金额:
    $ 29.44万
  • 项目类别:
    WBP Fellowship
Development of Peptide Chemical Modification Enabled by N-Halogenation of Amides
酰胺 N-卤化实现的肽化学修饰的发展
  • 批准号:
    22H02743
  • 财政年份:
    2022
  • 资助金额:
    $ 29.44万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Modulating Signaling Endocannabinoids and Fatty Acid Amides
调节信号传导内源性大麻素和脂肪酸酰胺
  • 批准号:
    10532252
  • 财政年份:
    2021
  • 资助金额:
    $ 29.44万
  • 项目类别:
CAREER: SusChEM: Iron Catalysts for the Reduction of Amides
职业:SusChEM:用于还原酰胺的铁催化剂
  • 批准号:
    2146728
  • 财政年份:
    2021
  • 资助金额:
    $ 29.44万
  • 项目类别:
    Continuing Grant
Modulating Signaling Endocannabinoids and Fatty Acid Amides
调节信号传导内源性大麻素和脂肪酸酰胺
  • 批准号:
    10399712
  • 财政年份:
    2021
  • 资助金额:
    $ 29.44万
  • 项目类别:
Nickel-Catalyzed Alpha-Arylation of Secondary Amides
镍催化仲酰胺的α-芳基化
  • 批准号:
    558383-2020
  • 财政年份:
    2020
  • 资助金额:
    $ 29.44万
  • 项目类别:
    Canadian Graduate Scholarships Foreign Study Supplements
Function of primary fatty acid amides as lipid mediators
伯脂肪酸酰胺作为脂质介质的功能
  • 批准号:
    20K21285
  • 财政年份:
    2020
  • 资助金额:
    $ 29.44万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
Catalytic Synthesis of Pharmaceutical Amides in Water
水中催化合成药用酰胺
  • 批准号:
    EP/T01430X/1
  • 财政年份:
    2020
  • 资助金额:
    $ 29.44万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了