Processivity and Catalytic Mechanism of Aldosterone Synthase

摘要 醛固酮的精细调节生产通过调节水和钠潴留来控制血压。 然而，醛固酮的过量产生导致原发性醛固酮增多症，继发性醛固酮增多症的主要形式是原发性醛固酮增多症。 高血压这种盐皮质激素由细胞色素P450 11B2（CYP 11B2）产生，也称为 作为醛固酮合成酶。虽然通过抑制CYP11B2降低醛固酮水平已被确立， 作为一种潜在的治疗方法，这种策略存在一些挑战。例如，CYP11B2 与产生皮质醇的P450 11 B1（CYP 11 B1）具有93%的序列同一性。尽管有相似之处 CYP11B1和CYP11B2之间存在关键的功能和结构差异。总的来说，这项研究 旨在了解这些微妙的差异如何有助于这些酶的催化功能， 帮助药物开发。

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.