Target Information
| Target General Information | Top | |||||
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| Target ID |
T50970
(Former ID: TTDR00135)
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| Target Name |
Endothelin-converting enzyme 1 (ECE1)
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| Synonyms |
ECE-1
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| Gene Name |
ECE1
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Converts big endothelin-1 to endothelin-1.
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.24.71
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| Sequence |
MRGVWPPPVSALLSALGMSTYKRATLDEEDLVDSLSEGDAYPNGLQVNFHSPRSGQRCWA
ARTQVEKRLVVLVVLLAAGLVACLAALGIQYQTRSPSVCLSEACVSVTSSILSSMDPTVD PCHDFFSYACGGWIKANPVPDGHSRWGTFSNLWEHNQAIIKHLLENSTASVSEAERKAQV YYRACMNETRIEELRAKPLMELIERLGGWNITGPWAKDNFQDTLQVVTAHYRTSPFFSVY VSADSKNSNSNVIQVDQSGLGLPSRDYYLNKTENEKVLTGYLNYMVQLGKLLGGGDEEAI RPQMQQILDFETALANITIPQEKRRDEELIYHKVTAAELQTLAPAINWLPFLNTIFYPVE INESEPIVVYDKEYLEQISTLINTTDRCLLNNYMIWNLVRKTSSFLDQRFQDADEKFMEV MYGTKKTCLPRWKFCVSDTENNLGFALGPMFVKATFAEDSKSIATEIILEIKKAFEESLS TLKWMDEETRKSAKEKADAIYNMIGYPNFIMDPKELDKVFNDYTAVPDLYFENAMRFFNF SWRVTADQLRKAPNRDQWSMTPPMVNAYYSPTKNEIVFPAGILQAPFYTRSSPKALNFGG IGVVVGHELTHAFDDQGREYDKDGNLRPWWKNSSVEAFKRQTECMVEQYSNYSVNGEPVN GRHTLGENIADNGGLKAAYRAYQNWVKKNGAEHSLPTLGLTNNQLFFLGFAQVWCSVRTP ESSHEGLITDPHSPSRFRVIGSLSNSKEFSEHFRCPPGSPMNPPHKCEVW Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T90ZS8 | |||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: 5-(2-hydroxyethyl)nonane-1,9-diol | Ligand Info | |||||
| Structure Description | structure of human ECE-1 complexed with phosphoramidon | PDB:3DWB | ||||
| Method | X-ray diffraction | Resolution | 2.38 Å | Mutation | Yes | [7] |
| PDB Sequence |
SEACVSVTSS
110 ILSSMDPTVD120 PCHDFFSYAC130 GGWIKANPVP140 DGHSRWGTFS150 NLWEHNQAII 160 KHLLENSTAS170 VSEAERKAQV180 YYRACMNETR190 IEELRAKPLM200 ELIERLGGWN 210 ITGPWAKDNF220 QDTLQVVTAH230 YRTSPFFSVY240 VSADSKNSNS250 NVIQVDQSGL 260 GLPSRDYYLN270 KTENEKVLTG280 YLNYMVQLGK290 LLGGGDEEAI300 RPQMQQILDF 310 ETALANITIP320 QEKRRDEELI330 YHKVTAAELQ340 TLAPAINWLP350 FLNTIFYPVE 360 INESEPIVVY370 DKEYLEQIST380 LINTTDRCLL390 NNYMIWNLVR400 KTSSFLDQRF 410 QDADEKFMEV420 MWKFCVSDTE440 NNLGFALGPM450 FVKATFAEDS460 KSIATEIILE 470 IKKAFEESLS480 TLKWMDEETR490 KSAKEKADAI500 YNMIGYPNFI510 MDPKELDKVF 520 NDYTAVPDLY530 FENAMRFFNF540 SWRVTADQLR550 KAPNRDQWSM560 TPPMVNAYYS 570 PTKNEIVFPA580 GILQAPFYTR590 SSPKALNFGG600 IGVVVGHELT610 HAFDDQGREY 620 DKDGNLRPWW630 KNSSVEAFKR640 QTECMVEQYS650 NYSVNGEPVN660 GRHTLGENIA 670 DNGGLKAAYR680 AYQNWVKKNG690 AEHSLPTLGL700 TNNQLFFLGF710 AQVWCSVRTP 720 ESSHEGLITD730 PHSPSRFRVI740 GSLSNSKEFS750 EHFRCPPGSP760 MNPPHKCEVW 770
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| Ligand Name: Phosphoramidon | Ligand Info | |||||
| Structure Description | structure of human ECE-1 complexed with phosphoramidon | PDB:3DWB | ||||
| Method | X-ray diffraction | Resolution | 2.38 Å | Mutation | Yes | [7] |
| PDB Sequence |
SEACVSVTSS
110 ILSSMDPTVD120 PCHDFFSYAC130 GGWIKANPVP140 DGHSRWGTFS150 NLWEHNQAII 160 KHLLENSTAS170 VSEAERKAQV180 YYRACMNETR190 IEELRAKPLM200 ELIERLGGWN 210 ITGPWAKDNF220 QDTLQVVTAH230 YRTSPFFSVY240 VSADSKNSNS250 NVIQVDQSGL 260 GLPSRDYYLN270 KTENEKVLTG280 YLNYMVQLGK290 LLGGGDEEAI300 RPQMQQILDF 310 ETALANITIP320 QEKRRDEELI330 YHKVTAAELQ340 TLAPAINWLP350 FLNTIFYPVE 360 INESEPIVVY370 DKEYLEQIST380 LINTTDRCLL390 NNYMIWNLVR400 KTSSFLDQRF 410 QDADEKFMEV420 MWKFCVSDTE440 NNLGFALGPM450 FVKATFAEDS460 KSIATEIILE 470 IKKAFEESLS480 TLKWMDEETR490 KSAKEKADAI500 YNMIGYPNFI510 MDPKELDKVF 520 NDYTAVPDLY530 FENAMRFFNF540 SWRVTADQLR550 KAPNRDQWSM560 TPPMVNAYYS 570 PTKNEIVFPA580 GILQAPFYTR590 SSPKALNFGG600 IGVVVGHELT610 HAFDDQGREY 620 DKDGNLRPWW630 KNSSVEAFKR640 QTECMVEQYS650 NYSVNGEPVN660 GRHTLGENIA 670 DNGGLKAAYR680 AYQNWVKKNG690 AEHSLPTLGL700 TNNQLFFLGF710 AQVWCSVRTP 720 ESSHEGLITD730 PHSPSRFRVI740 GSLSNSKEFS750 EHFRCPPGSP760 MNPPHKCEVW 770
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ARG145
4.874
PHE149
3.171
MET560
3.905
VAL565
2.506
ASN566
2.485
ALA567
2.778
TYR568
4.030
TYR569
4.686
ILE582
3.301
PHE587
4.467
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.98E-01 | Radiality | 1.34E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.50E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | Endothelin signaling pathway | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | SIDS Susceptibility Pathways | |||||
| 2 | Corticotropin-releasing hormone | |||||
| 3 | Endothelin Pathways | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Phosphinic tripeptides as dual angiotensin-converting enzyme C-domain and endothelin-converting enzyme-1 inhibitors. J Med Chem. 2010 Jan 14;53(1):208-20. | |||||
| REF 2 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 3 | The therapeutic potential of endothelin-1 receptor antagonists and endothelin-converting enzyme inhibitors on the cardiovascular system. Expert Opin Investig Drugs. 2002 Nov;11(11):1537-52. | |||||
| REF 4 | Endothelin-converting enzyme-1 inhibition and growth of human glioblastoma cells. J Med Chem. 2005 Jan 27;48(2):483-98. | |||||
| REF 5 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1615). | |||||
| REF 6 | Aminophosphonate endothelin converting enzyme inhibitors: potency-enhancing and selectivity-improving modifications of phosphoramidon, Bioorg. Med. Chem. Lett. 4(10):1257-1262 (1994). | |||||
| REF 7 | Structure of human endothelin-converting enzyme I complexed with phosphoramidon. J Mol Biol. 2009 Jan 9;385(1):178-87. | |||||
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