Date of Award
Master of Science in Chemical Sciences (MSCB)
Susan M. E. Smith
Michael Van Dyke
NADPH oxidases (NOX’s) are enzymes that catalyze the production of superoxide through single electron transfer. This superoxide production leads to the production of other reactive oxygen species (ROS). ROS affect many metabolic processes throughout the body that can cause several different diseases, making this an ideal target for drug discovery. The general structure of NOX contains a transmembrane (TM) domain and a dehydrogenase (DH) domain connected by a linker. The DH domain contains binding sites for FAD and NADPH/NADH that both participate in the electron transfer necessary for producing superoxide. Structural information of NOX’s is still relatively new to the scientific community. A recent structure of CsNOX (cyanobacterial NOX) provided new structural information, but atomic coordinate clashes between FAD, NADPH and multiple sidechains still raises questions on actual structural activity.1 The structural similarities within the NOX family make SpNOX (Streptococcus pneumoniae NOX), a bacterial NOX homolog with vigorous activity in detergents, ideal for use to identify NOX properties. Homologous to FNR, FAD is the end of the redox chain until its transfer to the hemes within the transmembrane domain. The FAD binding sites could serve as focus point in drug discovery for NOX’s. In this study, we examine the binding affinity of flavins (FAD, FMN, and riboflavin) to the DH domain of NOX.