M2: Angiotensin-converting enzymes (ACE and ACE2) | Enzymes

Home
Targets
Enzymes
Peptidases and proteinases
MA: Metallo (M) Peptidases
M2: Angiotensin-converting enzymes (ACE and ACE2)

M2: Angiotensin-converting enzymes (ACE and ACE2) C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Enzymes

ACE (Angiotensin-converting enzyme) C Show summary »« Hide summary More detailed page go icon to follow link

ACE2 (Angiotensin-converting enzyme 2) C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

1614

Nomenclature

Angiotensin-converting enzyme 2

Common abbreviation

ACE2

Previous and unofficial names

ACE-related carboxypeptidase | renal angiotensin-converting enzyme 2 | angiotensin I converting enzyme (peptidyl-dipeptidase A) 2

Genes

ACE2 (Hs), Ace2 (Mm), Ace2 (Rn)

Ensembl ID

ENSG00000130234 (Hs), ENSMUSG00000015405 (Mm), ENSRNOG00000031665 (Rn)

UniProtKB AC

Q9BYF1 (Hs), Q8R0I0 (Mm), Q5EGZ1 (Rn)

EC number

3.4.15.1

Binding dissociation constants for SARS-CoVs (Kd)

SARS-CoV-2 (1.2 nM); SARS-CoV (5 nM); Binding of hACE2 ectodomain to immobilised S^B domains of the viral strains in a biolayer interferometry assay. [14]

Endogenous substrates

angiotensin I (AGT, P01019) > angiotensin-(1-9) (AGT, P01019) [4]

Activators

XNT [PMID: 18391097] pEC₅₀ 4.7 [5]

Inhibitors

compound 28 [PMID: 18324760] pK_i 9.9 [11]

Selective inhibitors

MLN-4760 pIC₅₀ 9.4 [11]

References

Show »« Hide

1. Ceconi C, Francolini G, Olivares A, Comini L, Bachetti T, Ferrari R. (2007) Angiotensin-converting enzyme (ACE) inhibitors have different selectivity for bradykinin binding sites of human somatic ACE. Eur J Pharmacol, 577 (1-3): 1-6. [PMID:17716647]

2. Chevillard C, Jouquey S, Bree F, Mathieu MN, Stepniewski JP, Tillement JP, Hamon G, Corvol P. (1994) Compared properties of trandolapril, enalapril, and their diacid metabolites. J Cardiovasc Pharmacol, 23 Suppl 4: S11-5. [PMID:7527095]

3. DeForrest JM, Waldron TL, Harvey C, Scalese B, Rubin B, Powell JR, Petrillo EW, Cushman DW. (1989) Fosinopril, a phosphinic acid inhibitor of angiotensin I converting enzyme: in vitro and preclinical in vivo pharmacology. J Cardiovasc Pharmacol, 14 (5): 730-6. [PMID:2481187]

4. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R et al.. (2000) A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res, 87 (5): E1-9. [PMID:10969042]

5. Hernández Prada JA, Ferreira AJ, Katovich MJ, Shenoy V, Qi Y, Santos RA, Castellano RK, Lampkins AJ, Gubala V, Ostrov DA et al.. (2008) Structure-based identification of small-molecule angiotensin-converting enzyme 2 activators as novel antihypertensive agents. Hypertension, 51 (5): 1312-7. [PMID:18391097]

6. Kondoh G, Tojo H, Nakatani Y, Komazawa N, Murata C, Yamagata K, Maeda Y, Kinoshita T, Okabe M, Taguchi R et al.. (2005) Angiotensin-converting enzyme is a GPI-anchored protein releasing factor crucial for fertilization. Nat Med, 11 (2): 160-6. [PMID:15665832]

7. Krapcho J, Turk C, Cushman DW, Powell JR, DeForrest JM, Spitzmiller ER, Karanewsky DS, Duggan M, Rovnyak G, Schwartz J et al.. (1988) Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines. J Med Chem, 31 (6): 1148-60. [PMID:2836590]

8. Lefebvre HP, Brown SA, Chetboul V, King JN, Pouchelon JL, Toutain PL. (2007) Angiotensin-converting enzyme inhibitors in veterinary medicine. Curr Pharm Des, 13 (13): 1347-61. [PMID:17506720]

9. Leisle L, Parkin ET, Turner AJ, Hooper NM. (2005) Angiotensin-converting enzyme as a GPIase: a critical reevaluation. Nat Med, 11 (11): 1139-40. [PMID:16270062]

10. Michaud A, Williams TA, Chauvet MT, Corvol P. (1997) Substrate dependence of angiotensin I-converting enzyme inhibition: captopril displays a partial selectivity for inhibition of N-acetyl-seryl-aspartyl-lysyl-proline hydrolysis compared with that of angiotensin I. Mol Pharmacol, 51 (6): 1070-6. [PMID:9187274]

11. Mores A, Matziari M, Beau F, Cuniasse P, Yiotakis A, Dive V. (2008) Development of potent and selective phosphinic peptide inhibitors of angiotensin-converting enzyme 2. J Med Chem, 51 (7): 2216-26. [PMID:18324760]

12. Robinson DM, Curran MP, Lyseng-Williamson KA. (2007) Imidapril: a review of its use in essential hypertension, Type 1 diabetic nephropathy and chronic heart failure. Drugs, 67 (9): 1359-78. [PMID:17547476]

13. Sharma RK, Douglas RG, Louw S, Chibale K, Sturrock ED. (2012) New ketomethylene inhibitor analogues: synthesis and assessment of structural determinants for N-domain selective inhibition of angiotensin-converting enzyme. Biol Chem, 393 (6): 485-93. [PMID:22628311]

14. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. (2020) Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell, 181 (2): 281-292.e6. [PMID:32155444]

15. Waterfall JF. (1989) A review of the preclinical cardiovascular pharmacology of cilazapril, a new angiotensin converting enzyme inhibitor. Br J Clin Pharmacol, 27 Suppl 2: 139S-150S. [PMID:2527528]

16. Watermeyer JM, Kröger WL, O'Neill HG, Sewell BT, Sturrock ED. (2010) Characterization of domain-selective inhibitor binding in angiotensin-converting enzyme using a novel derivative of lisinopril. Biochem J, 428 (1): 67-74. [PMID:20233165]

How to cite this family page

Database page citation:

M2: Angiotensin-converting enzymes (ACE and ACE2). Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=741.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.