Evolutionarily Conserved Variations in Menaquinone Structure: Functional Implications

在化学系生命过程化学项目的支持下，科罗拉多州立大学的Debbie C. Crans、Dean C. Crick和Adam Chicco将研究电子传输系统对硫醌的利用。脂醌是一种含有氧化还原活性头基团和长脂类尾巴的分子。这两种分子成分赋予脂醌生物学上的基本特性，即在不同的生物分子（如酶）之间传递电子和质子的能力，以及成为疏水生物膜内部的一部分。这些特性使得脂醌对生物系统中的能量产生至关重要，因此对生命至关重要。研究小组将探索脂醌的结构如何影响它们所结合的酶，以及这些酶所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。该计划将汇集化学、微生物学和呼吸生理学领域的资深科学家和学生。各级学生，包括在科学领域代表性不足的少数民族，将获得跨学科的研究经验和技能以及科学传播技能。该项目将研究脂醌的结构和功能之间的联系，这是难以捉摸的。这些高度保守的甲基萘醌结构是细菌氧化磷酸化途径所必需的，其意义尚不清楚。使用Crans/Crick团队开发的工具，将采用多学科方法来确定细菌中脂醌的结构和功能之间的联系。Aim 1的研究将利用进化优化的电子传递系统评估合成和天然脂醌对原位氧化磷酸化（氧摄取）动力学的影响。目的2将侧重于测量脱氢酶和ATP合成酶对各种脂醌的底物亲和力。目的3将主要利用核磁共振波谱技术研究疏水环境中脂醌类化合物的结构表征。结构和功能数据将从硬脂结核棒状杆菌、分枝杆菌（以前归类为分枝杆菌）耻垢菌和粪肠球菌的研究中获得。该奖项反映了美国国家科学基金会的法定使命，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。

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.