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Discovery and characterization of ACE2 - a 20-year journey of surprises from vasopeptidase to COVID-19.
Clin Sci (Lond). 2020 Sep 30; 134(18):2489-2501.CS

Abstract

Angiotensin-converting enzyme (ACE) is a zinc membrane metallopeptidase that plays a key role in regulating vasoactive peptide levels and hence cardiovascular activity through its conversion of angiotensin I (Ang I) to Ang II and its metabolism of bradykinin. The discovery of its homologue, ACE2, 20 years ago has led to intensive comparisons of these two enzymes revealing surprising structural, catalytic and functional distinctions between them. ACE2 plays multiple roles not only as a vasopeptidase but also as a regulator of amino acid transport and serendipitously as a viral receptor, mediating the cellular entry of the coronaviruses causing severe acute respiratory syndrome (SARS) and, very recently, COVID-19. Catalytically, ACE2 functions as a monocarboxypeptidase principally converting the vasoconstrictor angiotensin II to the vasodilatory peptide Ang-(1-7) thereby counterbalancing the action of ACE on the renin-angiotensin system (RAS) and providing a cardioprotective role. Unlike ACE, ACE2 does not metabolise bradykinin nor is it inhibited by classical ACE inhibitors. However, it does convert a number of other regulatory peptides in vitro and in vivo. Interest in ACE2 biology and its potential as a possible therapeutic target has surged in recent months as the COVID-19 pandemic rages worldwide. This review highlights the surprising discoveries of ACE2 biology during the last 20 years, its distinctions from classical ACE and the therapeutic opportunities arising from its multiple biological roles.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Hooper NM
Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, U.K.
Lambert DW
School of Clinical Dentistry and Neuroscience Institute, University of Sheffield, Sheffield S10 2TA, U.K.
Turner AJ
School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT,U.K.

MeSH

Angiotensin IIAngiotensin-Converting Enzyme 2Angiotensin-Converting Enzyme InhibitorsBetacoronavirusCOVID-19Coronavirus InfectionsHumansPandemicsPeptidyl-Dipeptidase APneumonia, ViralRenin-Angiotensin SystemSARS-CoV-2Vasoconstrictor Agents

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32990314

Citation

Hooper, Nigel M., et al. "Discovery and Characterization of ACE2 - a 20-year Journey of Surprises From Vasopeptidase to COVID-19." Clinical Science (London, England : 1979), vol. 134, no. 18, 2020, pp. 2489-2501.
Hooper NM, Lambert DW, Turner AJ. Discovery and characterization of ACE2 - a 20-year journey of surprises from vasopeptidase to COVID-19. Clin Sci (Lond). 2020;134(18):2489-2501.
Hooper, N. M., Lambert, D. W., & Turner, A. J. (2020). Discovery and characterization of ACE2 - a 20-year journey of surprises from vasopeptidase to COVID-19. Clinical Science (London, England : 1979), 134(18), 2489-2501. https://doi.org/10.1042/CS20200476
Hooper NM, Lambert DW, Turner AJ. Discovery and Characterization of ACE2 - a 20-year Journey of Surprises From Vasopeptidase to COVID-19. Clin Sci (Lond). 2020 Sep 30;134(18):2489-2501. PubMed PMID: 32990314.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discovery and characterization of ACE2 - a 20-year journey of surprises from vasopeptidase to COVID-19. AU - Hooper,Nigel M, AU - Lambert,Daniel W, AU - Turner,Anthony J, PY - 2020/7/17/received PY - 2020/9/12/revised PY - 2020/9/15/accepted PY - 2020/9/29/entrez PY - 2020/9/30/pubmed PY - 2020/10/21/medline KW - COVID-19 KW - SARS KW - angiotensin converting enzyme 2 KW - coronavirus KW - metalloproteases KW - renin-angiotensin system SP - 2489 EP - 2501 JF - Clinical science (London, England : 1979) JO - Clin Sci (Lond) VL - 134 IS - 18 N2 - Angiotensin-converting enzyme (ACE) is a zinc membrane metallopeptidase that plays a key role in regulating vasoactive peptide levels and hence cardiovascular activity through its conversion of angiotensin I (Ang I) to Ang II and its metabolism of bradykinin. The discovery of its homologue, ACE2, 20 years ago has led to intensive comparisons of these two enzymes revealing surprising structural, catalytic and functional distinctions between them. ACE2 plays multiple roles not only as a vasopeptidase but also as a regulator of amino acid transport and serendipitously as a viral receptor, mediating the cellular entry of the coronaviruses causing severe acute respiratory syndrome (SARS) and, very recently, COVID-19. Catalytically, ACE2 functions as a monocarboxypeptidase principally converting the vasoconstrictor angiotensin II to the vasodilatory peptide Ang-(1-7) thereby counterbalancing the action of ACE on the renin-angiotensin system (RAS) and providing a cardioprotective role. Unlike ACE, ACE2 does not metabolise bradykinin nor is it inhibited by classical ACE inhibitors. However, it does convert a number of other regulatory peptides in vitro and in vivo. Interest in ACE2 biology and its potential as a possible therapeutic target has surged in recent months as the COVID-19 pandemic rages worldwide. This review highlights the surprising discoveries of ACE2 biology during the last 20 years, its distinctions from classical ACE and the therapeutic opportunities arising from its multiple biological roles. SN - 1470-8736 UR - https://www.unboundmedicine.com/medline/citation/32990314/Discovery_and_characterization_of_ACE2___a_20_year_journey_of_surprises_from_vasopeptidase_to_COVID_19_ DB - PRIME DP - Unbound Medicine ER -