LEAPS-MPS: Determining All the Contributions of Adrenodoxin to Cytochrome P450 Catalysis

LEAPS-MPS：确定肾上腺氧还蛋白对细胞色素 P450 催化的所有贡献

• 批准号: 2213207
• 负责人: Michael Reddish
• 金额: $ 24.98万
• 依托单位: Appalachian State University
• 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: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2213207&HistoricalAwards=false
• 关键词: LEAPS; MPS; Determining; Contributions; Adrenodoxin

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). In this project, funded by the Mathematical and Physical Sciences Directorate and housed in the Chemistry Division, Professor Michael Reddish and his students at Appalachian State University will investigate how a group of proteins, called ferredoxin proteins, enable cytochrome P450 enzymes to catalyze a wide range of chemical reactions in animals, plants, fungi, bacteria, and archaea. Cytochrome P450 enzymes naturally play a role in the metabolism of drugs, steroids, and other chemicals. Understanding how cytochrome P450 enzymes work enables the design of new medicines and more environmentally friendly industrial processes. Professor Reddish will also utilize resources from this project to: (1) Pay undergraduate students so they can meet their financial needs through research instead of external jobs; (2) Develop a new way to teach introductory chemistry that focuses on cohort-building so that all students feel welcome in science; and (3) Co-lead a course-based undergraduate research experience (CURE) in the upper-level biochemistry lab at Appalachian State University. These activities will enable more students to learn about research and encourage students with diverse histories to become researchers.Professor Reddish proposes to focus on the interactions of human cytochrome P450 27A1 and the human ferredoxin protein adrenodoxin. It is known that ferredoxin proteins supply electrons to cytochrome P450 enzymes. Evidence from various researchers suggests adrenodoxin may further promote catalysis in other ways. The project will include a structural approach to determine if adrenodoxin promotes catalysis by forcing the enzyme to a more “active” shape. The project will also test to see if adrenodoxin changes the functionality of the enzyme by altering ligand binding to the enzyme or altering reactivity of molecular oxygen utilized by the enzyme. It is proposed that a clear understanding of all roles of adrenodoxin in cytochrome P450 27A1 catalysis will allow for a better understanding of how other ferredoxins enable cytochrome P450 catalysis from a wide variety of sources and how their reactivity can be modified.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.

该奖项是根据2021年《美国救援计划法》（公法117-2）全部或部分资助的。在这个项目中，由数学和物理科学局资助并在化学部门内置，迈克尔·雷迪什（Michael Reddish）教授及其学生在阿巴拉契亚州立大学（Appalachian State University）将研究一组称为蛋白质蛋白的蛋白质，使细胞色素p450酶促进动物，植物，植物，饮食，a饮料，小吃和幼体的化学反应。细胞色素P450酶自然在药物，类固醇和其他化学物质的代谢中起作用。了解细胞色素P450酶的工作方式可以设计新药物和更环保的工业过程。 Reddish教授还将利用该项目的资源到：（1）支付本科生，以便他们可以通过研究而不是外部工作来满足其财务需求； （2）开发一种新的方式来教授介绍化学，重点是建造队列，以便所有学生都在科学方面受到欢迎； （3）在阿巴拉契亚州立大学的高层生物化学实验室中共同领导基于课程的本科研究经验（CURE）。这些活动将使更多的学生能够学习研究，并鼓励有潜水员历史的学生成为研究人员。专业人士Reddish提案专注于人类细胞色素P450 27A1和人类铁氧蛋白蛋白肾上腺素的相互作用。众所周知，铁氧还蛋白蛋白向细胞色素P450酶提供电子。来自各种研究人员的证据表明，肾上腺素毒素可能会以其他方式进一步促进催化。该项目将包括一种结构方法，以确定肾上腺素毒素是否通过迫使酶变为“活性”形状来促进催化。该项目还将测试以查看肾上腺素是通过改变配体与酶的结合或改变酶使用的分子氧的反应性来改变酶的功能。有人建议，对肾上腺素在细胞色素p450 27a1催化中的所有作用有清晰的了解，将使对其他铁毒素如何使细胞色素p450催化的方式更好地理解，从多种源中以及如何对其反应性进行了反应性，这些奖项是通过对NSF的法定任务和良好的支持的影响。 标准。