ACE2: from vasopeptidase to SARS virus receptor

Turner, Anthony J.; Hiscox, Julian A.; Hooper, Nigel M.

doi:10.1016/j.tips.2004.04.001

Cited by 509 publications

(506 citation statements)

References 26 publications

Supporting

Mentioning

489

Contrasting

Unclassified

Order By: Relevance

“…This view has recently been changed [5, 6] with the recognition that Ang-(1-7) is involved in apoptosis and growth arrest that antagonize the effect of Ang II [7]. Ang-(1-7) also interacts with a specific G protein-coupled receptor, the Mas receptor (MasR), present in several tissues, including heart and kidney [8,9,10]. However, the relevance of Ang-(1-7) to renal disease is still not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Renal ACE and ACE2 Expression in Early Diabetic Rats

Moon

Jeong²,

Lee³

et al. 2008

Nephron Exp Nephrol

View full text Add to dashboard Cite

AbstractBackground/Aim: The role of angiotensin-converting enzyme (ACE)-related carboxypeptidase-2 (ACE2) in the regulation of the renin-angiotensin system is not well characterized. This study investigated the changes in the expression of ACE and ACE2 in the kidney in early diabetic rats. Methods: Streptozotocin-induced diabetic rats were examined. The concentrations of angiotensin II in plasma, urine, and renal cortex were measured by radioimmunoassay. The mRNA expression of ACE, ACE2, angiotensin II type 1 receptor (AT1R), and Mas receptor (MasR) in glomeruli and cortex was assessed using real-time PCR. The glomerular and cortical expression of ACE and ACE2 was assessed by immunohistochemistry. Results: For renal cortical tissue, the angiotensin II level was more intensified in the 8-week diabetic rats. Immunohistochemical experiments showed that ACE was increased, but ACE2 was decreased in the glomeruli of 8-week diabetic rats, while both ACE and ACE2 in the tubules were increased. The AT1R mRNA in the glomeruli was decreased, while the MasR mRNA was increased in 2-week diabetic rats. Conclusion: The combined effects of increased ACE and decreased ACE2 in glomeruli may be associated with the activation of the renin-angiotensin system in early diabetic rats, which is known to increase proteinuria.

show abstract

Section: Introductionmentioning

confidence: 99%

Renal ACE and ACE2 Expression in Early Diabetic Rats

Moon

Jeong²,

Lee³

et al. 2008

Nephron Exp Nephrol

View full text Add to dashboard Cite

show abstract

“…Most recently, ACE2 has been identified as a functional receptor for the coronavirus which causes the severe acute respiratory syndrome (SARS) [14]. For recent reviews, see [15,16].ACE2 shares a number of characteristics with ACE, both being zinc-containing enzymes which are sensitive to anion activation [4,17,18]. However, unlike ACE, ACE2 functions as a carboxypeptidase and is not susceptible to inhibition by the classical ACE inhibitors [1,2].…”

mentioning

confidence: 99%

Identification of critical active‐site residues in angiotensin‐converting enzyme‐2 (ACE2) by site‐directed mutagenesis

Guy¹,

Jackson²,

Jensen³

et al. 2005

The FEBS Journal

115

121

View full text Add to dashboard Cite

Angiotensin-converting enzyme-2 (ACE2) is a membrane protein with its active site exposed to the extracellular surface of endothelial cells, the renal tubular epithelium and also the epithelia of the lung and the small intestine [1][2][3]. Here ACE2 is poised to metabolize circulating peptides which may include angiotensin II, a potent vasoconstrictor and the product of angiotensin I cleavage by angiotensin-converting enzyme (ACE; EC 3.4.15.1) [1,4]. Indeed, ACE2 has been implicated in the regulation of heart and renal function where it is proposed to control the concentrations of angiotensin II relative to its hypotensive metabolite, angiotensin-(1-7) [5][6][7][8][9][10][11][12][13]. Most recently, ACE2 has been identified as a functional receptor for the coronavirus which causes the severe acute respiratory syndrome (SARS) [14]. For recent reviews, see [15,16].ACE2 shares a number of characteristics with ACE, both being zinc-containing enzymes which are sensitive to anion activation [4,17,18]. However, unlike ACE, ACE2 functions as a carboxypeptidase and is not susceptible to inhibition by the classical ACE inhibitors [1,2]. After the elucidation of the crystal structure of testicular ACE (tACE), [19] a model of the active site of ACE2 was described which demonstrated the structural determinants underlying these differences in enzyme activity [17]. Critical residue substitutions were highlighted that gave rise to the elimination of the S2¢ pocket found in ACE such that ACE2 is able to remove only a single amino acid from the C-terminus of its substrates (whereas ACE is a peptidyl dipeptidase). Shortly after this, the structure of ACE2 was solved [20] which provided further insights into this enzyme in relation to its counterpart. However, it has Angiotensin-converting enzyme-2 (ACE2) may play an important role in cardiorenal disease and it has also been implicated as a cellular receptor for the severe acute respiratory syndrome (SARS) virus. The ACE2 activesite model and its crystal structure, which was solved recently, highlighted key differences between ACE2 and its counterpart angiotensin-converting enzyme (ACE), which are responsible for their differing substrate and inhibitor sensitivities. In this study the role of ACE2 active-site residues was explored by site-directed mutagenesis. Arg273 was found to be critical for substrate binding such that its replacement causes enzyme activity to be abolished. Although both His505 and His345 are involved in catalysis, it is His345 and not His505 that acts as the hydrogen bond donor ⁄ acceptor in the formation of the tetrahedral peptide intermediate. The difference in chloride sensitivity between ACE2 and ACE was investigated, and the absence of a second chloride-binding site (CL2) in ACE2 confirmed. Thus ACE2 has only one chloride-binding site (CL1) whereas ACE has two sites. This is the first study to address the differences that exist between ACE2 and ACE at the molecular level. The results can be applied to future studies aimed at unravelling the role of ACE2, ...

show abstract

“…The identification of angiotensin converting enzyme 2 (ACE2) as a host receptor for the SARS CoV has been confirmed [1096,1097] and CD290L, a C-type lectin also known as L-SIGN, DC-SIGNR and DC-SIGN2, has been identified as an additional receptor [1098]. Binding of SARS CoV to the ACE2 receptor has been mapped to the S1 domain of the trimeric SARS CoV spike protein while the C-type lectins also bind to the S protein of SARS CoV, but with lower efficiency than to ACE2.…”

Section: Sars Cov Biochemical Pharmacologymentioning

confidence: 96%

Developments in Antiviral Drug Design, Discovery and Development in 2004

Meanwell

Belema²,

Carini³

et al. 2005

CDTID

View full text Add to dashboard Cite

This article summarizes key aspects of progress made during 2004 toward the design, discovery and development of antiviral agents for clinical use. Important developments in the identification, characterization and clinical utility of inhibitors of human immunodeficiency virus; the hepatitis viruses, hepatitis B, hepatitis C; the herpes family of viruses, herpes simplex viruses 1 and 2, varicella zoster virus, Epstein-Barr virus and human cytomegalovirus; the respiratory viruses, influenza, respiratory syncytial virus, human metapneumovirus, picornaviruses, measles and the severe acute respiratory syndrome coronavirus; human papilloma virus; rotavirus; Ebola virus and West Nile virus, are reviewed.

show abstract

ACE2: from vasopeptidase to SARS virus receptor

Cited by 509 publications

References 26 publications

Renal ACE and ACE2 Expression in Early Diabetic Rats

Renal ACE and ACE2 Expression in Early Diabetic Rats

Identification of critical active‐site residues in angiotensin‐converting enzyme‐2 (ACE2) by site‐directed mutagenesis

Developments in Antiviral Drug Design, Discovery and Development in 2004

Contact Info

Product

Resources

About