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Review
. 2005 Aug 1;1751(1):2-8.
doi: 10.1016/j.bbapap.2004.10.010. Epub 2004 Nov 6.

Membrane-associated zinc peptidase families: comparing ACE and ACE2

J L Guy  1 , D W Lambert, F J Warner, N M Hooper, A J Turner
Affiliations
Review

Membrane-associated zinc peptidase families: comparing ACE and ACE2

J L Guy et al. Biochim Biophys Acta. .

Abstract

In contrast to the relatively ubiquitous angiotensin-converting enzyme (ACE), expression of the mammalian ACE homologue, ACE2, was initially described in the heart, kidney and testis. ACE2 is a type I integral membrane protein with its active site domain exposed to the extracellular surface of endothelial cells and the renal tubular epithelium. Here ACE2 is poised to metabolise circulating peptides which may include angiotensin II, a potent vasoconstrictor and the product of angiotensin I cleavage by ACE. To this end, ACE2 may counterbalance the effects of ACE within the renin-angiotensin system (RAS). Indeed, ACE2 has been implicated in the regulation of heart and renal function where it is proposed to control the levels of angiotensin II relative to its hypotensive metabolite, angiotensin-(1-7). The recent solution of the structure of ACE2, and ACE, has provided new insight into the substrate and inhibitor profiles of these two key regulators of the RAS. As the complexity of this crucial pathway is unravelled, there is a growing interest in the therapeutic potential of agents that modulate the activity of ACE2.

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Figures

Fig. 1
Fig. 1
Interaction of the catalytic sites of ACE2 and tACE with inhibitors. Schematic view of the binding interactions of (A) the inhibitor MLN-4760 at the active site of ACE2 (adapted from Ref. [18]) and (B) lisinopril at the active site of tACE (adapted from Ref. [11]). Hydrogen bonds to the ligand are shown (dotted lines). The different binding subsites are labelled.
Fig. 2
Fig. 2
Schematic representation of the renin–angiotensin system (RAS). ACE, angiotensin-converting enzyme; NEP, neprilysin; AT1, angiotensin II type I receptor; and AT2, angiotensin type II receptor. The conversion of angiotensin I to angiotensin-(1–9) by ACE2 is kinetically much less favourable than the conversion of angiotensin II to angiotensin-(1–7).
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References

    1. Turner A.J., Hooper N.M. The angiotensin-converting enzyme gene family: genomics and pharmacology. Trends Pharmacol. Sci. 2002;23:177. - PubMed
    1. Campbell D.J. Tissue renin–angiotensin system: sites of angiotensin formation. J. Cardiovasc. Pharmacol. 1987;10:S1–S8. - PubMed
    1. Skeggs L.T., Kahn J.R., Shumway N.P. The preparation and function of the hypertensin-converting enzyme. J. Exp. Biol. 1956;103:295–299. - PMC - PubMed
    1. Yang H.Y.T., Erdos E.G., Levin Y. A dipeptidyl carboxypeptidase that converts angiotensin I and inactivates bradykinin. Biochim. Biophys. Acta. 1970;214:374–376. - PubMed
    1. Tipnis S.R., Hooper N.M., Hyde R., Karran E., Christie G., Turner A.J. A human homologue of angiotensin-converting enzyme. J. Biol. Chem. 2000;275:33238. - PubMed

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