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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

基本信息

批准号：
1808495
负责人：
Holly Ellis
金额：
$ 52.5万
依托单位：
Auburn University
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：
2018-08-01 至 2021-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1808495&HistoricalAwards=false
关键词：
Mechanistic structural approaches sulfur acquisition

项目摘要

Many transformations that occur in nature are enhanced by enzymes. Enzymes play an important role in all of life processes, and use unique strategies to optimize the processes they catalyze. Often, enzymes involved in different chemical reactions incorporate similar strategies to ensure the reaction occurs. An important role of enzymes is maintaining appropriate levels of sulfur in the environment to sustain life. An intriguing aspect of enzymes that play a role in sulfur maintenance is that they utilize similar strategies and features, but are involved in different environmental reactions. For example, they all employ a version of riboflavin, vitamin B2. This award from the Chemistry of Life Processes Program in the Chemistry Division to Dr. Holly Ellis of Auburn University provides a unique opportunity to understand how essential enzymes that maintain environmental sulfur levels carry out their reactions. The experiments are designed to evaluate distinct features and strategies of these enzymes, which can be used to study other enzyme families. These investigations are providing graduate and undergraduate students with diverse scientific training and mentoring. Similar experimental techniques are being incorporated into a summer program for incoming freshman underrepresented in the STEM fields at Auburn University.The overall objective of the project is to determine how enzymes belonging to the same family utilize common structural motifs to catalyze different metabolic reactions. The enzymes that catalyze metabolic reactions utilized by bacteria to obtain sulfur have evolved a complex mechanism for sulfur acquisition. These reactions are vital in maintaining adequate cellular sulfur levels. The primary goal of these studies is to determine how the substrate specificity of the two-component FMN monooxygenases is maintained, and evaluate how the structural properties contribute to the specificity and desulfonation mechanism. The structural similarity of two-component FMN-dependent monooxygenases suggests that these enzymes utilize a similar innovative mechanism to catalyze carbon-sulfur bond cleavage. A comprehensive experimental approach is being employed to provide insight into the structure and functional properties of these enzyme systems. The studies proposed are utilizing a tractable system to evaluate a family of enzymes with similar structural and catalytic properties that are involved in a common metabolic goal. The studies described are providing an in-depth investigation on how the structural features of enzymes dictate function, and are providing innovative approaches that can be applied to other enzymes that utilize similar structural features.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.

自然界中发生的许多转化都是通过酶来增强的。酶在所有生命过程中发挥着重要作用，并使用独特的策略来优化它们催化的过程。通常，参与不同化学反应的酶会采用类似的策略来确保反应发生。酶的一个重要作用是维持环境中适当的硫含量以维持生命。在硫维持中发挥作用的酶的一个有趣的方面是它们利用相似的策略和特征，但参与不同的环境反应。例如，它们都使用一种核黄素，即维生素 B2。该奖项由化学系生命过程化学项目颁发给奥本大学的 Holly Ellis 博士，为了解维持环境硫水平的必需酶如何进行反应提供了独特的机会。这些实验旨在评估这些酶的独特特征和策略，可用于研究其他酶家族。这些调查为研究生和本科生提供了多样化的科学培训和指导。类似的实验技术正在被纳入奥本大学 STEM 领域的新生夏季项目中。该项目的总体目标是确定属于同一家族的酶如何利用共同的结构基序来催化不同的代谢反应。催化细菌利用代谢反应来获取硫的酶已经进化出复杂的硫获取机制。这些反应对于维持足够的细胞硫水平至关重要。这些研究的主要目标是确定如何维持双组分 FMN 单加氧酶的底物特异性，并评估结构特性如何影响特异性和脱磺化机制。双组分 FMN 依赖性单加氧酶的结构相似性表明这些酶利用类似的创新机制来催化碳硫键断裂。正在采用综合实验方法来深入了解这些酶系统的结构和功能特性。拟议的研究正在利用一个易于处理的系统来评估具有相似结构和催化特性的酶家族，这些酶涉及共同的代谢目标。所述研究对酶的结构特征如何决定功能进行了深入调查，并提供了可应用于利用类似结构特征的其他酶的创新方法。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。