ACE2: from vasopeptidase to SARS virus receptor

Abstract The zinc metallopeptidase angiotensin-converting enzyme 2 (ACE2) is the only known human homologue of the key regulator of blood pressure angiotensin-converting enzyme (ACE). Since its discovery in 2000, ACE2 has been implicated in heart function, hypertension and diabetes, with its effects being mediated, in part, through its ability to convert angiotensin II to angiotensin-(1–7). Unexpectedly, ACE2 also serves as the cellular entry point for the severe acute respiratory syndrome (SARS) virus and the enzyme is therefore a prime target for pharmacological intervention on several disease fronts.

[1]  D. Dimitrov,et al.  A model of the ACE2 structure and function as a SARS-CoV receptor , 2003, Biochemical and Biophysical Research Communications.

[2]  Wenhui Li,et al.  A 193-Amino Acid Fragment of the SARS Coronavirus S Protein Efficiently Binds Angiotensin-converting Enzyme 2* , 2004, Journal of Biological Chemistry.

[3]  Obi L. Griffith,et al.  The Genome Sequence of the SARS-Associated Coronavirus , 2003, Science.

[4]  C. Moorehead All rights reserved , 1997 .

[5]  Jodie L. Guy,et al.  Angiotensin-converting enzyme-2 (ACE2): comparative modeling of the active site, specificity requirements, and chloride dependence. , 2003, Biochemistry.

[6]  J. Hiscox The interaction of animal cytoplasmic RNA viruses with the nucleus to facilitate replication , 2003, Virus Research.

[7]  John L. Sullivan,et al.  Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus , 2003, Nature.

[8]  C. Berul,et al.  Heart block, ventricular tachycardia, and sudden death in ACE2 transgenic mice with downregulated connexins. , 2003, Journal of molecular and cellular cardiology.

[9]  D. Cavanagh Severe acute respiratory syndrome vaccine development: experiences of vaccination against avian infectious bronchitis coronavirus , 2003, Avian pathology : journal of the W.V.P.A.

[10]  J. Penninger,et al.  Enhanced Renal Immunocytochemical Expression of ANG-(1-7) and ACE2 During Pregnancy , 2003, Hypertension.

[11]  D. Dimitrov,et al.  The SARS-CoV S glycoprotein: expression and functional characterization , 2003, Biochemical and Biophysical Research Communications.

[12]  Christian Drosten,et al.  Characterization of a Novel Coronavirus Associated with Severe Acute Respiratory Syndrome , 2003, Science.

[13]  R. Natesh,et al.  Crystal structure of the human angiotensin-converting enzyme–lisinopril complex , 2003, Nature.

[14]  D. Averill,et al.  Cardiac Angiotensin-(1-7) in Ischemic Cardiomyopathy , 2003, Circulation.

[15]  James M. Gavin,et al.  Substrate-based design of the first class of angiotensin-converting enzyme-related carboxypeptidase (ACE2) inhibitors. , 2002, Journal of the American Chemical Society.

[16]  D. Diz,et al.  Counterregulatory actions of angiotensin-(1-7). , 1997, Hypertension.

[17]  M. Crackower,et al.  Angiotensin-converting enzyme 2 is an essential regulator of heart function , 2002, Nature.

[18]  K. Robison,et al.  A Novel Angiotensin-Converting Enzyme–Related Carboxypeptidase (ACE2) Converts Angiotensin I to Angiotensin 1-9 , 2000, Circulation research.

[19]  T. Parsons,et al.  Hydrolysis of Biological Peptides by Human Angiotensin-converting Enzyme-related Carboxypeptidase* , 2002, The Journal of Biological Chemistry.

[20]  A. Look,et al.  Human aminopeptidase N is a receptor for human coronavirus 229E , 1992, Nature.

[21]  James F. Riordan,et al.  Ace revisited: A new target for structure-based drug design , 2003, Nature Reviews Drug Discovery.

[22]  Matthew Ducar,et al.  Novel Peptide Inhibitors of Angiotensin-converting Enzyme 2* , 2003, The Journal of Biological Chemistry.

[23]  N. Hooper,et al.  The angiotensin-converting enzyme gene family: genomics and pharmacology. , 2002, Trends in pharmacological sciences.

[24]  Q. Lin,et al.  Increased Angiotensin-(1-7)–Forming Activity in Failing Human Heart Ventricles: Evidence for Upregulation of the Angiotensin-Converting Enzyme Homologue ACE2 , 2003, Circulation.

[25]  Nigel M. Hooper,et al.  A Human Homolog of Angiotensin-converting Enzyme , 2000, The Journal of Biological Chemistry.

[26]  C. Johnston,et al.  Characterization of Renal Angiotensin-Converting Enzyme 2 in Diabetic Nephropathy , 2003, Hypertension.

[27]  Saurabh Menon,et al.  ACE2 X-Ray Structures Reveal a Large Hinge-bending Motion Important for Inhibitor Binding and Catalysis , 2004, Journal of Biological Chemistry.