Coordinated Mechanistic Approaches to Desulfonation in Two-component FMN Monooxygenases

双组分 FMN 单加氧酶脱磺的协调机制方法

基本信息

  • 批准号:
    2105998
  • 负责人:
  • 金额:
    $ 52.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-02-01 至 2025-01-31
  • 项目状态:
    未结题

项目摘要

With support from the Chemistry of Life Processes Program in the Division of Chemistry, Professor Holly Ellis and her research team at East Carolina University will study the interesting chemistry carried out by some of the enzymes involved in the acquisition of the element sulfur that bacteria need for survival. A fascinating feature of these enzymes is their ability to change their structures to facilitate the reactions they catalyze. Many of these crucial structural changes and accompanying catalytic events are poorly understood. The two-component enzyme systems selected for this study utilize various structural changes to promote sulfur acquisition. Therefore, these enzyme systems will be ideal to evaluate a multitude of different structural strategies that would be essential for catalysis. The project will also be integrated with the Brody RISE Pre-College Program to train high school students from underrepresented groups in the sciences in different biochemical techniques used to understand enzyme function. An undergraduate student fellowship will be provided in the summer to mentor and encourage participation of underrepresented students in scientific research. Two-component flavin mononucleotide(FMN)-dependent monooxygenases are essential for sulfur acquisition in bacteria when preferred sulfur sources are limiting. These enzymes utilize an FMN reductase and monooxygenase to carry out their critical functional roles; roles that require an elegant coordinated mechanistic strategy for desulfonation. The described objectives will evaluate if the two-component flavin-dependent systems involved in sulfur acquisition have evolved common structural features and mechanistic steps to carry out their complex functional role. Objective 1 is to identify the mechanistic strategies of two-component FMN-dependent monooxygenases that promote desulfonation. Objective 2 is to determine how the structural properties of two-component NAD(P)H:FMN reductases dictate function. Both objectives utilize complementary spectroscopic, kinetic, and biophysical approaches to provide evidence for the desulfonation mechanism and identify oligomeric changes that contribute to flavin transfer in the NAD(P)H:FMN reductases.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.
在化学系生命过程化学项目的支持下,东卡罗莱纳大学的冬青埃利斯教授和她的研究小组将研究一些参与细菌生存所需的硫元素获取的酶所进行的有趣的化学反应。 这些酶的一个迷人的特征是它们能够改变它们的结构以促进它们催化的反应。 许多这些关键的结构变化和伴随的催化事件知之甚少。本研究选择的双组分酶系统利用各种结构变化来促进硫的获得。 因此,这些酶系统将是理想的,以评估许多不同的结构策略,将是必不可少的催化。该项目还将与Brody RISE大学预科项目相结合,以培养来自科学领域代表性不足的高中生,掌握用于了解酶功能的不同生化技术。将在夏季提供本科生奖学金,以指导和鼓励代表性不足的学生参与科学研究。 双组分黄素单甘肽(FMN)依赖性单加氧酶是必不可少的硫收购细菌时,首选的硫源是有限的。这些酶利用FMN还原酶和单加氧酶来执行它们的关键功能作用;这些作用需要优雅的协调机制策略来进行磺化。所描述的目标将评估,如果参与硫收购的双组分黄素依赖系统已经演变出共同的结构特征和机械步骤,以执行其复杂的功能作用。目的1是确定双组分FMN依赖性单加氧酶促进肌纤维化的机制策略。目的2是确定双组分NAD(P)H:FMN还原酶的结构特性如何决定功能。这两个目标利用互补的光谱,动力学和生物物理方法提供证据的磺化机制,并确定寡聚体的变化,有助于黄素转移的NAD(P)H:FMN reductases.This奖项反映了NSF的法定使命,并已被认为是值得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的支持。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Shorter Alkanesulfonate Carbon Chains Destabilize the Active Site Architecture of SsuD for Desulfonation
较短的烷磺酸盐碳链破坏了 SsuD 脱磺化活性位点结构的稳定性
  • DOI:
    10.1021/acs.biochem.2c00586
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Somai, Shruti;Yue, Kun;Acevedo, Orlando;Ellis, Holly R.
  • 通讯作者:
    Ellis, Holly R.
Oligomeric Changes Regulate Flavin Transfer in Two-Component FMN Reductases Involved in Sulfur Metabolism
  • DOI:
    10.1021/acs.biochem.3c00361
  • 发表时间:
    2023-08-31
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Aloh,Chioma H.;Zeczycki,Tonya N.;Ellis,Holly R.
  • 通讯作者:
    Ellis,Holly R.
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Holly Ellis其他文献

Holly Ellis的其他文献

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{{ truncateString('Holly Ellis', 18)}}的其他基金

Mechanistic and structural approaches for sulfur acquisition in the two-component FMN-dependent monooxygenases
双组分 FMN 依赖性单加氧酶中硫获取的机制和结构方法
  • 批准号:
    2133725
  • 财政年份:
    2021
  • 资助金额:
    $ 52.5万
  • 项目类别:
    Standard Grant
Mechanistic and structural approaches for sulfur acquisition in the two-component FMN-dependent monooxygenases
双组分 FMN 依赖性单加氧酶中硫获取的机制和结构方法
  • 批准号:
    1808495
  • 财政年份:
    2018
  • 资助金额:
    $ 52.5万
  • 项目类别:
    Standard Grant
Defining the Mechanistic Strategies of Defulfonation in the Alkanesulfonate Sulfonate Monooxygenase System
定义烷磺酸磺酸单加氧酶系统中去氟酰化的机制策略
  • 批准号:
    1244320
  • 财政年份:
    2013
  • 资助金额:
    $ 52.5万
  • 项目类别:
    Continuing Grant

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