N-domain of angiotensin-converting enzyme (ACE-N)

The N-domain of angiotensin-converting enzyme is one of two homologous domains found in somatic ACE, a zinc-dependent metallopeptidase critical for regulating blood pressure and electrolyte homeostasis via the renin–angiotensin and kallikrein–kinin systems. While both the N and C domains hydrolyze angiotensin I and bradykinin, the N-domain shows preferential activity toward certain substrates such as N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP), with implications in fibrosis and inflammation. Structural analysis reveals glycosylation is important for stability and function, and uniquely, the N-domain can also hydrolyze amyloid-beta fragments, suggesting relevance in neurodegenerative disease. Inhibitors targeting the N-domain, such as RXP407, are in development for new therapeutic applications (e.g., organ fibrosis). The detailed understanding of N-domain specificity provides a promising basis for design of safer, domain-selective ACE inhibitors for cardiovascular and potentially other indications[1][2][3][4][5][6][7].

Other names

N-domain of ACEACE-N domainN-terminal domain of angiotensin-converting enzymeN-ACE

Inhibition of metallopeptidase activity, blocking hydrolysis of physiological substrates such as N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP), bradykinin, angiotensin I, and amyloid-beta fragments[2][4][5][6]\nDomain-selective inhibition can modulate blood pressure and affect fibrosis or neurodegeneration depending on substrate specificity[2][7]