Molecular recognition and regulation of human angiotensin-I converting enzyme (ACE) activity by natural inhibitory peptides

Abstract

Angiotensin-I converting enzyme (ACE), a two-domain dipeptidylcarboxypeptidase, is a key regulator of blood pressure as a result of its critical role in the renin-angiotensin-aldosterone and kallikrein-kinin systems. Hence it is an important drug target in the treatment of cardiovascular diseases. ACE is primarily known for its ability to cleave angiotensin I (Ang I) to the vasoactive octapeptide angiotensin II (Ang II), but is also able to cleave a number of other substrates including the vasodilator bradykinin and N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP), a physiological modulator of hematopoiesis. For the first time we provide a detailed biochemical and structural basis for the domain selectivity of the natural peptide inhibitors of ACE, bradykinin potentiating peptide b and Ang II. Moreover, Ang II showed selective competitive inhibition of the carboxy-terminal domain of human somatic ACE providing evidence for a regulatory role in the human renin-angiotensin system (RAS).

Bioactive Constituents of the Silk Worm Bombyx mori

“…Angiotensin I converting enzyme (ACE) is an enzyme that catalyzes the cleavage of the inactive decapeptide angiotensin I to the active octapeptide angiotensin II, and this process is associated with an elevation of blood pressure [21]. Though a study on a group of Caucasians indicated that the ACE gene is not associated with genetic predisposition to high blood pressure [22], in recent years ACE inhibitors are used as antihypertensive drugs [21].…”

“…Though a study on a group of Caucasians indicated that the ACE gene is not associated with genetic predisposition to high blood pressure [22], in recent years ACE inhibitors are used as antihypertensive drugs [21]. The screening of natural ACE inhibitors is a hot research field aimed at ascertaining ways to treat cardiovascular diseases.…”

Angiotensin Converting Enzyme Regulates Cell Proliferation and Migration

“…[7] demonstrated that ACE behaves as a receptor for Ang-II triggering Ca 2+ signaling, through inositol 1,4,5-trisphosphate (InsP 3 ) formation. Accordingly, a binding site for Ang-II was described on ACE [9]. However, the role of Ang-II-mediated signaling through ACE is still unclear.…”

Efficient Calculation of Enzyme Reaction Free Energy Profiles Using a Hybrid Differential Relaxation Algorithm

“…ACE (Masuyer, Schwager, Sturrock, Isaac, & Acharya, 2012), aminopeptidase (Yang, Liu, Lin, & Li, 2013), and termolysin (Gumpena, Kishor, Ganji, & Addlagatta, 2011) are part of the same clan (CL0126) but they are grouped into two different families (PF01401 and PF01433).…”