Understanding how the distal pocket environment affects the ligand binding affinity of nitrite to heme proteins (1013.17)

Cardiovascular disease is the leading cause of death worldwide. Nitric oxide (NO) plays a fundamental role in cardiovascular health and disruptions in normal NO physiology is associated with the progression of cardiovascular disease. A relatively new mechanism by which heme proteins can support vasodilatation during hypoxia is by converting nitrite (NO2-) to NO. This NO2- reductase activity plays essential roles in a variety of physiological processes. Because there is a large range in NO2- affinity and NO2- reductase activity in heme proteins with the same active site, this research seeks to better understand how the protein environment controls the binding chemistry of NO2- to the heme active site. Our goal is to determine how the distal pocket environment affects the binding affinity of NO2- to metmyoglobin mutants. Our hypothesis is that the distal pocket environment can increase the binding affinity of NO2- by way of electrostatic and steric interactions. To do this, we will compare the binding affin...