Target Information
| Target General Information | Top | |||||
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| Target ID |
T94879
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| Target Name |
HUMAN phosphodiesterase type 5 (PDE5)
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| Synonyms |
cGMP-specific 3',5'-cyclic phosphodiesterase; PDE5A; CGMP-binding cGMP-specific phosphodiesterase; CGB-PDE
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| Gene Name |
PDE5A
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| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Sexual dysfunction [ICD-11: HA00-HA01] | |||||
| Function |
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP. Specifically regulates nitric-oxide-generated cGMP.
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| BioChemical Class |
Phosphoric diester hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 3.1.4.35
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| Sequence |
MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKATREMVNAWFAE
RVHTIPVCKEGIRGHTESCSCPLQQSPRADNSAPGTPTRKISASEFDRPLRPIVVKDSEG TVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLI SADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPL NIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDE KDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIIS FMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTME PLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGK VKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETREL QSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWIL SVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGV NNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAI LATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAE LVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCF PLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Drugs in Phase 3 Trial | [+] 1 | + | ||||
| 1 | Sildenafil | Drug Info | Approved | Erectile dysfunction | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | Sildenafil | Drug Info | [1], [3] | |||
| 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: Tadalafil | Ligand Info | |||||
| Structure Description | Catalytic Domain Of Human Phosphodiesterase 5A In Complex With Tadalafil | PDB:1XOZ | ||||
| Method | X-ray diffraction | Resolution | 1.37 Å | Mutation | Yes | [4] |
| PDB Sequence |
EEETRELQSL
543 AAAVVPSAQT553 LKITDFSFSD563 FELSDLETAL573 CTIRMFTDLN583 LVQNFQMKHE 593 VLCRWILSVK603 KNYRKNVAYH613 NWRHAFNTAQ623 CMFAALKAGK633 IQNKLTDLEI 643 LALLIAALSH653 DLDHPGVSNQ663 FLINTNSELA673 LMYNDESVLE682 HHHFDQCLMI 692 LNSPGNQILS702 GLSIEEYKTT712 LKIIKQAILA722 TDLALYIKRR732 GEFFELIRKN 742 QFNLEDPHQK752 ELFLAMLMTA762 CDLSAITKPW772 PIQQRIAELV782 ATEFFDQGDR 792 ERKELNIEPT802 DLMNREKKNK812 IPSMQVGFID822 AICLQLYEAL832 THVSEDCFPL 842 LDGCRKNRQK852 WQALAE
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Vardenafil | Ligand Info | |||||
| Structure Description | Catalytic Domain Of Human Phosphodiesterase 5A In Complex With Vardenafil | PDB:1XP0 | ||||
| Method | X-ray diffraction | Resolution | 1.79 Å | Mutation | Yes | [4] |
| PDB Sequence |
EEETRELQSL
543 AAAVVPSAQT553 LKITDFSFSD563 FELSDLETAL573 CTIRMFTDLN583 LVQNFQMKHE 593 VLCRWILSVK603 KNYRKNVAYH613 NWRHAFNTAQ623 CMFAALKAGK633 IQNKLTDLEI 643 LALLIAALSH653 DLDHPGVSNQ663 FLINTNSELA673 LMYNDESVLE682 HHHFDQCLMI 692 LNSPGNQILS702 GLSIEEYKTT712 LKIIKQAILA722 TDLALYIKRR732 GEFFELIRKN 742 QFNLEDPHQK752 ELFLAMLMTA762 CDLSAITKPW772 PIQQRIAELV782 ATEFFDQGDR 792 ERKELNIEPT802 DLMNREKKNK812 IPSMQVGFID822 AICLQLYEAL832 THVSEDCFPL 842 LDGCRKNRQK852 WQALAE
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TYR612
3.717
HIS613
4.245
LEU725
4.056
ASP764
4.992
LEU765
3.863
ALA767
3.759
ILE768
3.806
GLN775
4.249
ILE778
4.639
ALA779
3.771
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| 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).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
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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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| Purine metabolism | hsa00230 | Affiliated Target |
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| Class: Metabolism => Nucleotide metabolism | Pathway Hierarchy | ||
| cGMP-PKG signaling pathway | hsa04022 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Chemical Structure based Activity Landscape of Target | Top |
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| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| References | Top | |||||
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| REF 1 | Nitric oxide inhibits the replication cycle of severe acute respiratory syndrome coronavirus. J Virol. 2005 Feb;79(3):1966-9. doi: 10.1128/JVI.79.3.1966-1969.2005. | |||||
| REF 2 | FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 206401. | |||||
| REF 3 | Any possible role of phosphodiesterase type 5 inhibitors in the treatment of severe COVID19 infections A lesson from urology. Clin Immunol. 2020 May;214:108414. | |||||
| REF 4 | Structural basis for the activity of drugs that inhibit phosphodiesterases. Structure. 2004 Dec;12(12):2233-47. | |||||
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