Angiotensin-converting enzyme (C-domain) (ACE-C)

Angiotensin-converting enzyme (ACE) is a zinc-dependent dicarboxypeptidase that plays a pivotal role in the renin-angiotensin-aldosterone system (RAAS) by regulating blood pressure and fluid balance [1]. The somatic form of ACE consists of two homologous catalytic domains, the N-domain and the C-domain, each possessing a distinct active site [2]. The C-domain is the dominant site for the conversion of Angiotensin I to the potent vasoconstrictor Angiotensin II in vivo, making it the primary target for antihypertensive therapy [3]. Although conventional ACE inhibitors like lisinopril and enalapril are non-selective and bind to both domains, research into C-domain-preferring inhibitors aims to refine therapeutic outcomes [4]. Specifically, selective C-domain inhibition seeks to maintain the blood-pressure-lowering effects of Angiotensin II reduction while potentially avoiding the side effects associated with N-domain inhibition, such as the accumulation of bradykinin which can lead to a persistent dry cough and angioedema [2,3]. This target is central to managing conditions like hypertension, heart failure, and diabetic nephropathy by modulating vascular tone and sodium retention [1,4]. Sources: [1] UniProt Consortium. UniProtKB - P12821 (ACE_HUMAN). [2] Fuchs, S., et al. (2004). Role of the N-terminal catalytic domain of angiotensin-converting enzyme. PubMed: 15153603. [3] Masuyer, G., et al. (2012). Molecular basis of lisinopril-variant binding to human angiotensin-I-converting enzyme. PubMed: 22432438. [4] Herman, L. L., et al. (2023). Angiotensin Converting Enzyme Inhibitors (ACEI). StatPearls.

Other names

ACE C-domainSomatic ACE C-terminal domainPeptidyl-dipeptidase AACE1 C-domainAngiotensin-converting enzyme, C-domain-preferring

Competitive inhibition of the C-domain catalytic site of angiotensin-converting enzyme, preventing the conversion of Angiotensin I to the potent vasoconstrictor Angiotensin II.