Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T94879 | Target Info | |||
| Target Name | HUMAN phosphodiesterase type 5 (PDE5) | ||||
| Synonyms | cGMP-specific 3',5'-cyclic phosphodiesterase; PDE5A; CGMP-binding cGMP-specific phosphodiesterase; CGB-PDE | ||||
| Gene Name | PDE5A | ||||
| Biochemical Class | Phosphoric diester hydrolase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Rhucin | Ligand Info | |||
| Canonical SMILES | CCCC1=NN(C2=C1N=C(NC2=O)C3=C(C=CC(=C3)S(=O)(=O)N4CCN(CC4)C)OCC)C | ||||
| InChI | 1S/C22H30N6O4S/c1-5-7-17-19-20(27(4)25-17)22(29)24-21(23-19)16-14-15(8-9-18(16)32-6-2)33(30,31)28-12-10-26(3)11-13-28/h8-9,14H,5-7,10-13H2,1-4H3,(H,23,24,29) | ||||
| InChIKey | BNRNXUUZRGQAQC-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 135398744 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 1TBF Catalytic Domain Of Human Phosphodiesterase 5A in Complex with Sildenafil | ||||||
| Method | X-ray diffraction | Resolution | 1.30 Å | Mutation | Yes | [1] |
| 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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| PDB ID: 3JWQ Crystal structure of chimeric PDE5/PDE6 catalytic domain complexed with sildenafil | ||||||
| Method | X-ray diffraction | Resolution | 2.87 Å | Mutation | No | [2] |
| PDB Sequence |
ETRELQSLAA
545 AVVPSAQTLK555 ITDFSFSDFE565 LSDLETALCT575 IRMFTDLNLV585 QNFQMKHEVL 595 CRWILSVKKN605 YRKNVAYHNW615 RHAFNTAQCM625 FAALKAGKIQ635 NKLTDLEILA 645 LLIAALSHDL655 DHRGVNNSYI665 QRSEHPLAQL675 YCHSIMEHHH685 FDQCLMILNS 695 PGNQILSGLS705 IEEYKTTLKI715 IKQAILATDL725 ALYIKRRGEF735 FELIRKNQFN 745 LEDPHQKELF755 LAMLMTACDL765 SAITKPWPIQ775 QRIAELVATE785 FWEQGDLERT 795 VLQQQPIPMM805 DRNKRDELPK815 LQVGFIDFVC825 TQLYEALTHV835 SEDCFPLLDG 845 CRKNRQKWQA855 LAEQ
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TYR612
3.583
HIS613
3.925
LEU725
3.995
LEU765
4.181
ALA767
4.466
ILE768
4.605
GLN775
4.872
ILE778
4.651
ALA779
4.409
VAL782
3.864
|
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| PDB ID: 2H42 Crystal structure of PDE5 in complex with sildenafil | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [3] |
| PDB Sequence |
EETRELQSLA
544 AAVVPSAQTL554 KITDFSFSDF564 ELSDLETALC574 TIRMFTDLNL584 VQNFQMKHEV 594 LCRWILSVKK604 NYRKNVAYHN614 WRHAFNTAQC624 MFAALKAGKI634 QNKLTDLEIL 644 ALLIAALSHD654 LDHRGVNNSY664 IQRSEHPLAQ674 LYCHSIMEHH684 HFDQCLMILN 694 SPGNQILSGL704 SIEEYKTTLK714 IIKQAILATD724 LALYIKRRGE734 FFELIRKNQF 744 NLEDPHQKEL754 FLAMLMTACD764 LSAITKPWPI774 QQRIAELVAT784 EFFDQGDRER 794 KELNIEPTDL804 MNREKKNKIP814 SMQVGFIDAI824 CLQLYEALTH834 VSEDCFPLLD 844 GCRKNRQKWQ854 ALAEQQ
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TYR612
3.878
HIS613
3.898
ASN661
3.378
ASN662
4.030
SER663
3.918
ILE665
4.462
LEU725
4.054
ASP764
4.844
LEU765
4.038
ALA767
3.657
ILE768
3.953
GLN775
4.496
|
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| PDB ID: 1UDT Crystal structure of Human Phosphodiesterase 5 complexed with Sildenafil(Viagra) | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [4] |
| PDB Sequence |
TRELQSLAAA
546 VVPSAQTLKI556 TDFSFSDFEL566 SDLETALCTI576 RMFTDLNLVQ586 NFQMKHEVLC 596 RWILSVKKNY606 RKNVAYHNWR616 HAFNTAQCMF626 AALKAGKIQN636 KLTDLEILAL 646 LIAALSHDLD656 HRGVNNSYYC677 HSIMEHHHFD687 QCLMILNSPG697 NQILSGLSIE 707 EYKTTLKIIK717 QAILATDLAL727 YIKRRGEFFE737 LIRKNQFNLE747 DPHQKELFLA 757 MLMTACDLSA767 ITKPWPIQQR777 IAELVATEFF787 DQGDRERKEL797 NIEPTDLMNR 807 EKKNKIPSMQ817 VGFIDAICLQ827 LYEALTHVSE837 DCFPLLDGCR847 KNRQKWQALA 857 EQQ
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .VIA or .VIA2 or .VIA3 or :3VIA;style chemicals stick;color identity;select .A:612 or .A:613 or .A:661 or .A:663 or .A:664 or .A:725 or .A:764 or .A:765 or .A:767 or .A:768 or .A:775 or .A:779 or .A:782 or .A:783 or .A:786 or .A:804 or .A:813 or .A:816 or .A:817 or .A:819 or .A:820 or .A:823 or .A:824; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TYR612
3.447
HIS613
3.787
ASN661
3.663
SER663
4.307
TYR664
3.185
LEU725
4.509
ASP764
4.904
LEU765
4.210
ALA767
3.986
ILE768
3.714
GLN775
4.631
ALA779
3.042
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases. Mol Cell. 2004 Jul 23;15(2):279-86. | ||||
| REF 2 | Structural basis of phosphodiesterase 6 inhibition by the C-terminal region of the gamma-subunit. EMBO J. 2009 Nov 18;28(22):3613-22. | ||||
| REF 3 | Multiple conformations of phosphodiesterase-5: implications for enzyme function and drug development. J Biol Chem. 2006 Jul 28;281(30):21469-21479. | ||||
| REF 4 | Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. Nature. 2003 Sep 4;425(6953):98-102. | ||||
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