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

The **Angiotensin-converting enzyme C-domain** (ACE C-domain, cACE) is one of two homologous catalytic domains in the membrane-bound or soluble forms of angiotensin-converting enzyme (ACE), a key zinc-dependent metallopeptidase in the renin–angiotensin–aldosterone system[2][5][8]. This domain is primarily responsible for converting angiotensin I to angiotensin II, a potent vasoconstrictor, making it crucial for blood pressure and extracellular fluid regulation[3][6]. While both N- and C-domains contribute to bradykinin degradation, the C-domain is chiefly responsible for angiotensin II production in vivo[4][6]. The C-domain is the main pharmacological target of ACE inhibitor drugs, which block its function to lower blood pressure and treat cardiovascular and renal diseases[3][2]. Crystal structures reveal its catalytic mechanism depends on a conserved zinc-binding motif and distinct substrate recognition features compared to the N-domain[1][2]. Selective C-domain inhibition is under investigation due to the possibility that it can reduce hypertension while minimizing side effects like cough and angioedema that arise from bradykinin accumulation when both domains are inhibited[6].

Other names

C-domain of angiotensin-converting enzymecACEACE-CACE C-terminal domain

Inhibition of enzyme’s catalytic site, reducing conversion of angiotensin I to angiotensin II; Decreasing angiotensin II levels (leading to vasodilation and lower blood pressure); Increased bradykinin availability (due to less degradation); Selective C-domain inhibition may spare some N-domain substrates, potentially improving safety profiles