What’s new in the renin-angiotensin system?

Abstract

Angiotensin-converting enzyme-2 (ACE2) is the first human homologue of ACE to be described. ACE2 is a type I integral membrane protein which functions as a carboxypeptidase, cleaving a single hydrophobic/basic residue from the C-terminus of its substrates. ACE2 efficiently hydrolyses the potent vasoconstrictor angiotensin II to angiotensin (1-7). It is a consequence of this action that ACE2 participates in the renin-angiotensin system. However, ACE2 also hydrolyses dynorphin A (1-13), apelin-13 and des-Arg(9) bradykinin. The role of ACE2 in these peptide systems has yet to be revealed. A physiological role for ACE2 has been implicated in hypertension, cardiac function, heart function and diabetes, and as a receptor of the severe acute respiratory syndrome coronavirus. This paper reviews the biochemistry of ACE2 and discusses key findings such as the elucidation of crystal structures for ACE2 and testicular ACE and the development of ACE2 inhibitors that have now provided a basis for future research on this enzyme.

Potential interventions for novel coronavirus in China: A systematic review

“…Angiotensin-converting enzyme-2 (ACE2) is a type I integral membrane protein which functions as a carboxypeptidase and is the first human homolog of ACE. 84 ACE2 efficiently hydrolyzes the potent vasoconstrictor angiotensin II to angiotensin (1-7) and it has been implicated in hypertension, cardiac function, heart function, and diabetes. 84 In addition, ACE2 is also a functional receptor of SARS-CoV and it mediates virus entry into the cell through binding with spike (S) protein.…”

“…84 ACE2 efficiently hydrolyzes the potent vasoconstrictor angiotensin II to angiotensin (1-7) and it has been implicated in hypertension, cardiac function, heart function, and diabetes. 84 In addition, ACE2 is also a functional receptor of SARS-CoV and it mediates virus entry into the cell through binding with spike (S) protein. 85,86 The S protein of SARS-CoV is a type I surface glycoprotein and is responsible for the binding to cellular receptors.…”

Expanding role for the apelin/APJ system in physiopathology

“…Therefore, since ACE is known as an essential regulator of the Renin-Angiotensin-Aldosterone system, ACE2 has to be considered in the interplay between angiotensin and apelin, and to participate with ACE to the regulation of cardiovascular and renal functions (69). To pour more complexity, ACE2 is an integral membrane protein also hydrolyzing several other peptides, and described as a receptor for the severe acute respiratory syndrome coronavirus (96). ACE2 is neither inhibited by benzylsuccinate, a carboxypeptidase inhibitor, nor by other ACE inhibitors (32).…”

ACE2, the Receptor that Enables Infection by SARS‐CoV‐2: Biochemistry, Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators

“…[2][3][4][5][6] An earlier review had a focus on biochemistry, including details of ACE2 glycosylation, substrate specificity, the requirement for pH and Cl À for activity. [7] Here we review the structural and biochemical information on ACE2, analyse its dynamics and allosteric properties, and assess the possibility of identifying small compounds able to disrupt the interaction with SARS-CoV-2 allosterically.…”