Evolutionarily Conserved Variations in Menaquinone Structure: Functional Implications

Colorado State University, Fort Collins CO

Investigators

Abstract

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.