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

来自新墨西哥大学健康科学中心的冯长建博士将在化学系生命过程化学项目中研究一氧化氮合酶（NOS）的作用机制。这种风味血红蛋白负责一氧化氮（NO）的生物合成，一氧化氮是一种普遍存在的分子，参与调节几种生理过程。真核NOS同工型是含有黄素单核苷酸（FMN）和血红素结构域的大型模块化酶，由钙调素结合连接体连接。令人信服的证据表明FMN/血红素对接在NOS调控中的重要性。然而，FMN结构域在NOS催化中的分子机制尚不清楚。这个问题将通过脉冲电子顺磁共振（EPR）、激光闪光光解和诱变方法的综合方案来解决。由于新墨西哥大学是一所西班牙裔服务机构，该奖项将为未被充分代表的少数民族提供研究机会，包括来自新墨西哥州和其他州其他机构的本科生。我们将努力与那些申请联邦拨款的总体成功率历来较低的机构取得联系。

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.