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

Angiotensin-converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase that plays a central role in the renin-angiotensin system by converting angiotensin I to the potent vasoconstrictor angiotensin II and degrading the vasodilator bradykinin [1, 11]. Somatic ACE consists of two homologous catalytic domains, the N-domain and the C-domain, which exhibit distinct substrate specificities and physiological roles [1, 3]. The N-domain is uniquely responsible for the degradation of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), a natural tetrapeptide that inhibits hematopoietic stem cell proliferation and possesses potent anti-fibrotic properties [4, 7]. While both domains can produce angiotensin II, the C-domain is the primary site for this conversion in vivo, making the N-domain an attractive target for therapeutic strategies aimed at increasing Ac-SDKP levels to treat fibrosis or provide myeloprotection during chemotherapy without causing profound hypotension [2, 8]. Selective N-domain inhibitors, such as the experimental phosphinic peptide RXP407, have demonstrated the potential to modulate these specific pathways while sparing the C-domain's primary role in blood pressure regulation [4, 6].

Other names

N-terminal domain of ACEACE1 N-domainPeptidyl-dipeptidase A N-domainSomatic ACE N-domain

Selective inhibition of the N-terminal catalytic domain of angiotensin-converting enzyme