Abstract The finely tuned production of aldosterone controls blood pressure by regulating water and sodium retention. The overproduction of aldosterone, however, leads to primary aldosteronism, the major form of secondary hypertension. This mineralocorticoid hormone is produced by cytochrome P450 11B2 (CYP11B2), also known as aldosterone synthase. While lowering aldosterone levels through inhibition of CYP11B2 has been established as a potential therapeutic approach, a few challenges are associated with this tactic. For example, CYP11B2 shares a 93% sequence identity with the cortisol-producing P450 11B1 (CYP11B1). Despite the similarities between CYP11B1 and CYP11B2, there exist key functional and structural differences. Overall, this research aims to understand how these subtle differences contribute to the catalytic function of these enzymes in order to aid drug development.

Project Narrative Primary aldosteronism (PA), although once considered a rare disease, is estimated to affect 5-10% of patients with hypertension. This illness is characterized by uncontrolled aldosterone production by cytochrome P450 11B2 (CYP11B2). Given the lack of current treatments and the high incidence of cardiovascular (heart failure, stroke, tachycardia…) events in patients with PA, it is pivotal to understand the reactions catalyzed by CYP11B2 to assist aid drug development.