Processivity and Catalytic Mechanism of Aldosterone Synthase

NIH RePORTER · NIH · F31 · $19,986 · view on reporter.nih.gov ↗

Abstract

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.

Key facts

NIH application ID
10763821
Project number
5F31GM149006-02
Recipient
UNIVERSITY OF MICHIGAN AT ANN ARBOR
Principal Investigator
Juan Jose Valentin-Goyco
Activity code
F31
Funding institute
NIH
Fiscal year
2024
Award amount
$19,986
Award type
5
Project period
2023-01-05 → 2024-05-02