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黛比·C·克兰斯、迪恩·C·克里克和亚当·奇科将研究电子传输系统对脂醌的利用。脂醌是含有氧化还原活性的头部基团和长的类脂尾巴的分子。这两个分子组分赋予脂醌生物基本性质，即在酶等不同生物分子之间传递电子和质子的能力，以及成为疏水性生物膜内部的一部分的能力。这些性质使得脂醌对生物系统中的能量生产至关重要，从而对生命也是必不可少的。该团队将探索脂醌的结构如何影响它们与之结合的酶以及这些酶参与的电子传递过程。这项研究旨在阐明在细菌中进化优化的电子传输系统中化学和生物学之间的基本联系。拟议的项目将把化学、微生物学和呼吸生理学的资深科学家和学生聚集在一起。所有水平的学生，包括科学界代表性较低的少数族裔，将获得跨学科的研究经验和技能以及科学交流技能。该项目将研究脂醌的结构和功能之间的联系，这是一个难以捉摸的问题。这些高度保守的菜籽酮结构在细菌中的氧化磷酸化途径中所需的意义尚不清楚。将采用多学科方法，使用CRANS/Crick团队开发的工具来确定细菌中脂醌的结构和功能之间的联系。目标1的研究将使用进化优化的电子传输系统评估合成的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将重点研究脱氢酶和三磷酸腺苷合成酶对各种脂醌的底物亲和力。目标3将主要利用核磁共振波谱对脂醌在疏水环境中的结构特征进行研究。结构和功能数据将从对结核杆菌、污垢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智力优势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.