Target Information
| Target General Information | Top | |||||
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| Target ID |
T83979
(Former ID: TTDI02539)
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| Target Name |
Prostacyclin synthase (PTGIS)
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| Synonyms |
Prostaglandin I2 synthase; PTGIS
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| Gene Name |
PTGIS
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2).
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| BioChemical Class |
Intramolecular oxidoreductases
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| UniProt ID | ||||||
| EC Number |
EC 5.3.99.4
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| Sequence |
MAWAALLGLLAALLLLLLLSRRRTRRPGEPPLDLGSIPWLGYALDFGKDAASFLTRMKEK
HGDIFTILVGGRYVTVLLDPHSYDAVVWEPRTRLDFHAYAIFLMERIFDVQLPHYSPSDE KARMKLTLLHRELQALTEAMYTNLHAVLLGDATEAGSGWHEMGLLDFSYSFLLRAGYLTL YGIEALPRTHESQAQDRVHSADVFHTFRQLDRLLPKLARGSLSVGDKDHMCSVKSRLWKL LSPARLARRAHRSKWLESYLLHLEEMGVSEEMQARALVLQLWATQGNMGPAAFWLLLFLL KNPEALAAVRGELESILWQAEQPVSQTTTLPQKVLDSTPVLDSVLSESLRLTAAPFITRE VVVDLAMPMADGREFNLRRGDRLLLFPFLSPQRDPEIYTDPEVFKYNRFLNPDGSEKKDF YKDGKRLKNYNMPWGAGHNHCLGRSYAVNSIKQFVFLVLVHLDLELINADVEIPEFDLSR YGFGLMQPEHDVPVRYRIRP Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A05962 | |||||
| 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: Minoxidil | Ligand Info | |||||
| Structure Description | Crystal structure of human prostacyclin synthase in complex with inhibitor minoxidil | PDB:3B6H | ||||
| Method | X-ray diffraction | Resolution | 1.62 Å | Mutation | No | [2] |
| PDB Sequence |
RTRRPGEPPL
32 DLGSIPWLGY42 ALDFGKDAAS52 FLTRMKEKHG62 DIFTILVGGR72 YVTVLLDPHS 82 YDAVVWEPRT92 RLDFHAYAIF102 LMERIFDVQL112 PHYSPSDEKA122 RMKLTLLHRE 132 LQALTEAMYT142 NLHAVLLGDA152 TEAGSGWHEM162 GLLDFSYSFL172 LRAGYLTLYG 182 IEALPRTHES192 QAQDRVHSAD202 VFHTFRQLDR212 LLPKLARGSL222 SVGDKDHMCS 232 VKSRLWKLLS242 PARLARRAHR252 SKWLESYLLH262 LEEMGVSEEM272 QARALVLQLW 282 ATQGNMGPAA292 FWLLLFLLKN302 PEALAAVRGE312 LESILWQLPQ332 KVLDSTPVLD 342 SVLSESLRLT352 AAPFITREVV362 VDLAMPMADG372 REFNLRRGDR382 LLLFPFLSPQ 392 RDPEIYTDPE402 VFKYNRFLNP412 DGSEKKDFYK422 DGKRLKNYNM432 PWGAGHNHCL 442 GRSYAVNSIK452 QFVFLVLVHL462 DLELINADVE472 IPEFDLSRYG482 FGLMQPEHDV 492 PVRYRIRPH
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| Ligand Name: B-Octylglucoside | Ligand Info | |||||
| Structure Description | Crystal structure of human prostacyclin synthase in complex with inhibitor minoxidil | PDB:3B6H | ||||
| Method | X-ray diffraction | Resolution | 1.62 Å | Mutation | No | [2] |
| PDB Sequence |
RTRRPGEPPL
32 DLGSIPWLGY42 ALDFGKDAAS52 FLTRMKEKHG62 DIFTILVGGR72 YVTVLLDPHS 82 YDAVVWEPRT92 RLDFHAYAIF102 LMERIFDVQL112 PHYSPSDEKA122 RMKLTLLHRE 132 LQALTEAMYT142 NLHAVLLGDA152 TEAGSGWHEM162 GLLDFSYSFL172 LRAGYLTLYG 182 IEALPRTHES192 QAQDRVHSAD202 VFHTFRQLDR212 LLPKLARGSL222 SVGDKDHMCS 232 VKSRLWKLLS242 PARLARRAHR252 SKWLESYLLH262 LEEMGVSEEM272 QARALVLQLW 282 ATQGNMGPAA292 FWLLLFLLKN302 PEALAAVRGE312 LESILWQLPQ332 KVLDSTPVLD 342 SVLSESLRLT352 AAPFITREVV362 VDLAMPMADG372 REFNLRRGDR382 LLLFPFLSPQ 392 RDPEIYTDPE402 VFKYNRFLNP412 DGSEKKDFYK422 DGKRLKNYNM432 PWGAGHNHCL 442 GRSYAVNSIK452 QFVFLVLVHL462 DLELINADVE472 IPEFDLSRYG482 FGLMQPEHDV 492 PVRYRIRPH
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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).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
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
Human Pathway Affiliation
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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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Arachidonic acid metabolism | hsa00590 | Affiliated Target |
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| Class: Metabolism => Lipid metabolism | Pathway Hierarchy | ||
| Degree | 6 | Degree centrality | 6.45E-04 | Betweenness centrality | 1.03E-04 |
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| Closeness centrality | 1.99E-01 | Radiality | 1.34E+01 | Clustering coefficient | 6.67E-01 |
| Neighborhood connectivity | 9.67E+00 | Topological coefficient | 2.84E-01 | 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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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| References | Top | |||||
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| REF 1 | Role of prostacyclin synthase in carcinogenesis. Prostaglandins Other Lipid Mediat. 2017 Nov;133:49-52. | |||||
| REF 2 | Structures of prostacyclin synthase and its complexes with substrate analog and inhibitor reveal a ligand-specific heme conformation change. J Biol Chem. 2008 Feb 1;283(5):2917-26. | |||||
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