Evolutionarily Conserved Variations in Menaquinone Structure: Functional Implications

甲基萘醌结构的进化保守变异：功能意义

• 批准号: 2204265
• 负责人: Debbie Crans
• 金额: $ 52.8万
• 依托单位: Colorado State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2204265&HistoricalAwards=false
• 关键词: Evolutionarily; Conserved; Variations; Menaquinone; Structure

With the support of the Chemistry of Life Processes Program in the Division of Chemistry, Debbie C. Crans, Dean C. Crick, and Adam Chicco from Colorado State University will study the utilization of lipoquinone by electron transport systems. Lipoquinones are molecules that contain a redox active head group and a long lipid-like tail. These two molecular components confer biologically essential properties upon lipoquinones, namely the ability to transport electrons and protons between different biomolecules such as enzymes and to be part of the hydrophobic biological membrane interior. These properties make lipoquinones essential for energy production in biological systems and consequently for life. The team will explore how the structure of lipoquinones affects the enzyme to which they bind and the electron transport processes in which the enzymes are involved. The research aims to elucidate the fundamental link between chemistry and biology in evolutionarily optimized electron transport systems in bacteria. The proposed project will bring together senior scientists and students in chemistry, microbiology, and respiratory physiology. Students at all levels, including underrepresented minorities in science, will gain interdisciplinary research experience and skills as well as science communication skills.The project will investigate the link between the structure and function of lipoquinones, which is elusive. The significance of these highly conserved menaquinone structures that are required for oxidative phosphorylation pathways in bacteria has remained unclear. A multidisciplinary approach will be taken to determine the link between structure and function of lipoquinones in bacteria using tools developed by the Crans/Crick team. Studies in Aim 1 will assess the impact of synthetic and native lipoquinone on the kinetics of in situ oxidative phosphorylation (oxygen uptake) using evolutionarily optimized electron transport systems. Aim 2 will focus on the measurement of the substrate affinity of dehydrogenases and ATP synthase for various lipoquinones. Aim 3 will focus on the structural characterization of lipoquinones in hydrophobic environments using mainly NMR spectroscopy. Structural and functional data will be obtained from studies of Corynebacterium tuberculostearicum, Mycolicibacterium (previously categorized as Mycobacterium) Smegmatis and Enterococcus faecalis.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，Debbie C. Dean C. Crans来自科罗拉多州立大学的Crick和Adam Chicco将研究电子传递系统对Lipoquinone的利用。 脂质醌是含有氧化还原活性头部基团和长的脂质样尾部的分子。 这两种分子组分赋予脂醌生物学上的基本性质，即在不同生物分子如酶之间传输电子和质子的能力，以及成为疏水生物膜内部的一部分的能力。 这些性质使得脂醌对于生物系统中的能量产生以及因此对于生命是必不可少的。该团队将探索脂醌的结构如何影响它们结合的酶以及酶参与的电子传递过程。该研究旨在阐明细菌中进化优化的电子传递系统中化学和生物学之间的基本联系。拟议的项目将汇集化学，微生物学和呼吸生理学的高级科学家和学生。各个级别的学生，包括科学领域代表性不足的少数族裔，将获得跨学科研究经验和技能以及科学沟通技能。该项目将调查脂醌的结构和功能之间的联系，这是难以捉摸的。细菌中氧化磷酸化途径所需的这些高度保守的甲基萘醌结构的意义仍然不清楚。将采取多学科方法，使用Crans/Crick团队开发的工具来确定细菌中lipoquinones的结构和功能之间的联系。 目标1中的研究将使用进化优化的电子传递系统评估合成和天然的脂醌对原位氧化磷酸化（氧摄取）动力学的影响。目的2将集中于对各种脂醌的脱氢酶和ATP合酶的底物亲和力的测量。 目标3将集中在结构表征的脂醌在疏水环境中，主要使用核磁共振光谱。 结构和功能数据将从对结核硬脂棒状杆菌、分枝杆菌（以前被归类为Smegalocyte分枝杆菌）和粪肠球菌的研究中获得。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。