Membrane-associated zinc peptidase families: comparing ACE and ACE2.
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.
Guy
J L
JL
Proteolysis Research Group, School of Biochemistry and Microbiology, University of Leeds, Leeds, LS2 9JT, UK.
Lambert
D W
DW
Warner
F J
FJ
Hooper
N M
NM
Turner
A J
AJ
D000595:Amino Acid Sequence; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002268:Carboxypeptidases / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism; D013379:Substrate Specificity
D000806:Angiotensin-Converting Enzyme Inhibitors; D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D002268:Carboxypeptidases; C104431:Ance protein, Drosophila; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; D008666:Metalloendopeptidases