Mechanism of nitric oxide synthase regulation by interdomain FMN/heme docking

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In this award from the Chemistry of Life Processes Program in the Division of Chemistry, Dr. Changjian Feng, from the University of New Mexico Health Sciences Center, will investigate the mechanism of action of the enzyme nitric oxide synthase (NOS). This flavo-hemoprotein is responsible for the biosynthesis of nitric oxide (NO), a ubiquitous molecule involved in the regulation of several physiological processes. Eukaryotic NOS isoforms are large modular enzymes containing flavin mononucleotide (FMN) and heme domains connected by a calmodulin-binding linker. Compelling evidence shows the importance of interdomain FMN/heme docking in the regulation of NOS. However, the molecular mechanism by which the FMN domain functions in NOS catalysis is unclear. This problem will be tackled by an integrated program of pulsed electron paramagnetic resonance (EPR), laser flash photolysis, and mutagenesis approaches. Because the University of New Mexico is a Hispanic serving institution, this award will provide research opportunities to underrepresented minorities, including undergraduate students from other institutions in New Mexico and other states. Efforts will be made to reach out to institutions in which the aggregate success rate for applications to federal grants has been low historically.