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Angiotensin-converting enzyme

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Target not currently curated in GtoImmuPdb

Target id: 1613

Nomenclature: Angiotensin-converting enzyme

Abbreviated Name: ACE

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

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 1306 17q23.3 ACE angiotensin I converting enzyme
Mouse 1 1312 11 68.84 cM Ace angiotensin I converting enzyme (peptidyl-dipeptidase A) 1
Rat 1 1313 10q32.1 Ace angiotensin I converting enzyme
Previous and Unofficial Names Click here for help
CD143 | Kininase II | Dipeptidyl carboxypeptidase 1 | DCP1
Database Links Click here for help
Specialist databases
MEROPS M02.001 (Hs)
Other databases
Alphafold P12821 (Hs), P09470 (Mm), P47820 (Rn)
BRENDA 3.4.15.1
ChEMBL Target CHEMBL1808 (Hs), CHEMBL2994 (Mm), CHEMBL2625 (Rn)
DrugBank Target P12821 (Hs)
Ensembl Gene ENSG00000159640 (Hs), ENSMUSG00000020681 (Mm), ENSRNOG00000062101 (Rn)
Entrez Gene 1636 (Hs), 11421 (Mm), 24310 (Rn)
Human Protein Atlas ENSG00000159640 (Hs)
KEGG Enzyme 3.4.15.1
KEGG Gene hsa:1636 (Hs), mmu:11421 (Mm), rno:24310 (Rn)
OMIM 106180 (Hs)
Orphanet ORPHA117728 (Hs)
Pharos P12821 (Hs)
RefSeq Nucleotide NM_001178057 (Hs), NM_152830 (Hs), NM_000789 (Hs), NM_207624 (Mm), NM_009598 (Mm), NM_012544 (Rn)
RefSeq Protein NP_001171528 (Hs), NP_690043 (Hs), NP_000780 (Hs), NP_997507 (Mm), NP_033728 (Mm), NP_036676 (Rn)
SynPHARM 78463 (in complex with captopril)
78474 (in complex with enalaprilat)
78461 (in complex with lisinopril)
80724 (in complex with RXP-407)
UniProtKB P12821 (Hs), P09470 (Mm), P47820 (Rn)
Wikipedia ACE (Hs)
Enzyme Reaction Click here for help
EC Number: 3.4.15.1
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
Ac-SDKP N/A - -
Hip-His Leu Hs Km 2.51x10-3 M pKm 2.6 5
Endogenous substrates (Human)
angiotensin I (AGT, P01019) > angiotensin II (AGT, P01019)

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
lisinopril Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 9.4 pKi 12
⤷ pKi 9.4 (Ki 3.6x10-10 M) [12]
zofenoprilat Small molecule or natural product Approved drug Ligand has a PDB structure Oc Inhibition 9.4 pKi 9
⤷ pKi 9.4 (Ki 4x10-10 M) [9]
captopril Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.4 pKi 12
⤷ pKi 8.4 (Ki 3.98x10-9 M) [12]
fasidotrilat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.0 pKi 1
⤷ pKi 8.0 (Ki 9.8x10-9 M) [1]
spiraprilat Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 9.1 pIC50 15
⤷ pIC50 9.1 (IC50 8x10-10 M) [15]
perindoprilat Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 9.0 pIC50 2
⤷ pIC50 9.0 (IC50 1.05x10-9 M) [2]
benazepril Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 8.8 pIC50 16
⤷ pIC50 8.8 (IC50 1.7x10-9 M) [16]
imidaprilat Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 8.7 pIC50 13
⤷ pIC50 8.7 (IC50 2x10-9 M) [13]
cilazaprilat Small molecule or natural product Approved drug Primary target of this compound Oc Inhibition 8.7 pIC50 17
⤷ pIC50 8.7 (IC50 1.9x10-9 M) [17]
quinaprilat Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 8.5 pIC50 7
⤷ pIC50 8.5 (IC50 2.9x10-9 M) [7]
trandolaprilat Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.5 pIC50 3
⤷ pIC50 8.5 (IC50 3.2x10-9 M) [3]
temocaprilat Small molecule or natural product Oc Inhibition 8.4 pIC50 19
⤷ pIC50 8.4 (IC50 3.6x10-9 M) [19]
Description: Inhibition of ACE activity, using hippuryl-histidyl-leucine as substrate, and ACE from rabbit lung.
ramiprilat Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 8.4 pIC50 11
⤷ pIC50 8.4 (IC50 4.2x10-9 M) [11]
moexiprilat Small molecule or natural product Approved drug Oc Inhibition 8.2 pIC50 6
⤷ pIC50 8.2 (IC50 6.5x10-9 M) [6]
lisinopril-tryptophan Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.2 pIC50 18
⤷ pIC50 8.2 (IC50 6.6x10-9 M) C-domain assay [18]
RXP-407 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.1 pIC50 14
⤷ pIC50 8.1 (IC50 7x10-9 M) N-domain selective inhibition [14]
quinapril Small molecule or natural product Approved drug Cp Inhibition 8.1 pIC50 8
⤷ pIC50 8.1 (IC50 8.3x10-9 M) [8]
zofenoprilat Small molecule or natural product Approved drug Ligand has a PDB structure Rn Inhibition 8.1 pIC50 9
⤷ pIC50 8.1 (IC50 8x10-9 M) [9]
fosinoprilat Small molecule or natural product Approved drug Ligand has a PDB structure Oc Inhibition 8.0 pIC50 4
⤷ pIC50 8.0 (IC50 1.1x10-8 M) [4]
trandolapril Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 7.8 pIC50 3
⤷ pIC50 7.8 (IC50 1.5x10-8 M) [3]
ramipril Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 7.6 pIC50 11
⤷ pIC50 7.6 (IC50 2.6x10-8 M) [11]
enalaprilat Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.5 pIC50 3
⤷ pIC50 7.5 (IC50 3.4x10-8 M) [3]
benazeprilat Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 6.6 pIC50 10
⤷ pIC50 6.6 (IC50 2.8x10-7 M) [10]
enalapril Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 4.3 pIC50 3
⤷ pIC50 4.3 (IC50 5x10-5 M) [3]
perindopril Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition - -
⤷
imidapril Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition - -
⤷
fosinopril Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition - -
⤷
cilazapril Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition - -
⤷
zofenopril Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition - -
⤷
fasidotril Small molecule or natural product Click here for species-specific activity table Hs Inhibition - -
⤷
moexipril Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition - -
⤷
spirapril Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition - -
⤷
View species-specific inhibitor tables
Immuno Process Associations
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 1 GO processes
GO:0002474 antigen processing and presentation of peptide antigen via MHC class I TAS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
click arrow to show/hide IEA associations
GO:0050729 positive regulation of inflammatory response IEA
Immuno Process:  Immune system development
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
click arrow to show/hide IEA associations
GO:0050729 positive regulation of inflammatory response IEA
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Acetm4Keb|Bdkrb2tm1Jfh Acetm4Keb/Acetm4Keb,Bdkrb2tm1Jfh/Bdkrb2tm1Jfh
involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ		 MGI:102845  MGI:87874  MP:0000530 abnormal kidney vasculature morphology PMID: 12637363 
Acetm4Keb|Bdkrb2tm1Jfh Acetm4Keb/Acetm4Keb,Bdkrb2tm1Jfh/Bdkrb2tm1Jfh
involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ		 MGI:102845  MGI:87874  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 12637363 
Acetm4Keb|Bdkrb2tm1Jfh Acetm4Keb/Acetm4Keb,Bdkrb2tm1Jfh/Bdkrb2tm1Jfh
involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ		 MGI:102845  MGI:87874  MP:0000208 decreased hematocrit PMID: 12637363 
Acetm4Keb|Bdkrb2tm1Jfh Acetm4Keb/Acetm4Keb,Bdkrb2tm1Jfh/Bdkrb2tm1Jfh
involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ		 MGI:102845  MGI:87874  MP:0003918 decreased kidney weight PMID: 12637363 
Acetm4Keb|Bdkrb2tm1Jfh Acetm4Keb/Acetm4Keb,Bdkrb2tm1Jfh/Bdkrb2tm1Jfh
involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ		 MGI:102845  MGI:87874  MP:0006264 decreased systemic arterial systolic blood pressure PMID: 12637363 
Acetm4Keb|Bdkrb2tm1Jfh Acetm4Keb/Acetm4Keb,Bdkrb2tm1Jfh/Bdkrb2tm1Jfh
involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ		 MGI:102845  MGI:87874  MP:0002988 decreased urine osmolality PMID: 12637363 
Acetm4Keb|Bdkrb2tm1Jfh Acetm4Keb/Acetm4Keb,Bdkrb2tm1Jfh/Bdkrb2tm1Jfh
involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ		 MGI:102845  MGI:87874  MP:0003675 kidney cysts PMID: 12637363 
Acetm4Keb|Bdkrb2tm1Jfh Acetm4Keb/Acetm4Keb,Bdkrb2tm1Jfh/Bdkrb2tm1Jfh
involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ		 MGI:102845  MGI:87874  MP:0001864 vasculitis PMID: 12637363 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Microvascular complications of diabetes, susceptibility to, 3; MVCD3
OMIM: 612624
Disease:  Renal tubular dysgenesis
OMIM: 267430
Orphanet: ORPHA97369
Disease:  Stroke, hemorrhagic
OMIM: 614519

References

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1. Abbenante G, Fairlie DP. (2005) Protease inhibitors in the clinic. Med Chem, 1 (1): 71-104. [PMID:16789888]

2. 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]

3. 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]

4. 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]

5. Eyries M, Michaud A, Deinum J, Agrapart M, Chomilier J, Kramers C, Soubrier F. (2001) Increased shedding of angiotensin-converting enzyme by a mutation identified in the stalk region. J Biol Chem, 276 (8): 5525-32. [PMID:11076943]

6. Friehe H, Ney P. (1997) Pharmacological and toxicological studies of the new angiotensin converting enzyme inhibitor moexipril hydrochloride. Arzneimittelforschung, 47 (2): 132-44. [PMID:9079232]

7. Hausin RJ, Codding PW. (1991) Molecular and crystal structures of MDL27,467A hydrochloride and quinapril hydrochloride, two ester derivatives of potent angiotensin converting enzyme inhibitors. J Med Chem, 34 (2): 511-7. [PMID:1995872]

8. Kaplan HR, Cohen DM, Essenburg AD, Major TC, Mertz TE, Ryan MJ. (1984) CI-906 and CI-907: new orally active nonsulfhydryl angiotensin-converting enzyme inhibitors. Fed Proc, 43 (5): 1326-9. [PMID:6323223]

9. 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]

10. 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]

11. Metzger H, Maier R, Sitter C, Stern HO. (1984) 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S) -2-azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498)--a new and highly effective angiotensin I converting enzyme inhibitor. Arzneimittelforschung, 34 (10B): 1402-6. [PMID:6097265]

12. 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]

13. 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]

14. 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]

15. Smith EM, Swiss GF, Neustadt BR, McNamara P, Gold EH, Sybertz EJ, Baum T. (1989) Angiotensin converting enzyme inhibitors: spirapril and related compounds. J Med Chem, 32 (7): 1600-6. [PMID:2544729]

16. Stanton JL, Watthey JW, Desai MN, Finn BM, Babiarz JE, Tomaselli HC. (1985) Angiotensin converting enzyme inhibitors: structure-activity profile of 1-benzazepin-2-one derivatives. J Med Chem, 28 (11): 1603-6. [PMID:2999394]

17. 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]

18. 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]

19. Yanagisawa H, Ishihara S, Ando A, Kanazaki T, Miyamoto S, Koike H, Iijima Y, Oizumi K, Matsushita Y, Hata T. (1987) Angiotensin-converting enzyme inhibitors: perhydro-1,4-thiazepin-5-one derivatives. J Med Chem, 30 (11): 1984-91. [PMID:3669006]

How to cite this page

M2: Angiotensin-converting enzymes (ACE and ACE2): Angiotensin-converting enzyme. Last modified on 04/10/2021. Accessed on 28/01/2023. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1613.