Binding Site Information of Target
| 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 | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| 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 | [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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| 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 | [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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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 | ||||||
| Ligand Name: Rhucin | Ligand Info | |||||
| Structure Description | Catalytic Domain Of Human Phosphodiesterase 5A in Complex with Sildenafil | PDB:1TBF | ||||
| Method | X-ray diffraction | Resolution | 1.30 Å | Mutation | Yes | [2] |
| 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 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: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:824; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Avanafil | Ligand Info | |||||
| Structure Description | Human PDE5 catalytic core in complex with avanafil | PDB:6L6E | ||||
| Method | X-ray diffraction | Resolution | 1.92 Å | Mutation | No | [3] |
| 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 FFDQGDRERK 795 ELNIEPTDLM805 NREKKNKIPS815 MQVGFIDAIC825 LQLYEALTHV835 SEDCFPLLDG 845 CRKNRQKWQA855 LAEQ
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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 .E6L or .E6L2 or .E6L3 or :3E6L;style chemicals stick;color identity;select .A:612 or .A:725 or .A:729 or .A:765 or .A:767 or .A:768 or .A:775 or .A:778 or .A:779 or .A:782 or .A:783 or .A:786 or .A:787 or .A:804 or .A:813 or .A:816 or .A:817 or .A:820 or .A:824; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Guanosine-5'-Monophosphate | Ligand Info | |||||
| Structure Description | Catalytic Domain Of Human Phosphodiesterase 5A in Complex with GMP | PDB:1T9S | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [2] |
| 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 Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5GP or .5GP2 or .5GP3 or :35GP;style chemicals stick;color identity;select .A:612 or .A:613 or .A:617 or .A:653 or .A:654 or .A:657 or .A:723 or .A:725 or .A:764 or .A:765 or .A:768 or .A:775 or .A:779 or .A:782 or .A:786 or .A:804 or .A:816 or .A:817 or .A:820; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Isobutylmethylxanthine | Ligand Info | |||||
| Structure Description | Crystal structure of PDE5A1-IBMX | PDB:1RKP | ||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | Yes | [4] |
| 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 QQRLAELVAT784 EFFDQGDREK 809 KNKIPSMQVG819 FIDAICLQLY829 EALTHVSEDC839 FPLLDGCRKN849 RQKWQALAEQ 859 Q
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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 .IBM or .IBM2 or .IBM3 or :3IBM;style chemicals stick;color identity;select .A:612 or .A:613 or .A:660 or .A:725 or .A:764 or .A:765 or .A:767 or .A:768 or .A:775 or .A:782 or .A:786 or .A:816 or .A:817 or .A:820; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 5-ethoxy-4-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)thiophene-2-sulfonamide | Ligand Info | |||||
| Structure Description | Crystal structure of the PDE5A catalytic domain in complex with a novel inhibitor | PDB:3BJC | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [5] |
| 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 EFFDQGDREK 809 KNKIPSMQVG819 FIDAICLQLY829 EALTHVSEDC839 FPLLDGCRKN849 RQKWQALAEQ 859 Q
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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 .WAN or .WAN2 or .WAN3 or :3WAN;style chemicals stick;color identity;select .A:612 or .A:613 or .A:660 or .A:725 or .A:764 or .A:765 or .A:767 or .A:768 or .A:775 or .A:778 or .A:779 or .A:782 or .A:783 or .A:786 or .A:787 or .A:813 or .A:816 or .A:817 or .A:820; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 2-[(4-Chlorophenyl)methyl]-5-methoxy-3,10-diazatricyclo[6.4.1.0^{4,13}]trideca-1,4(13),5,7-tetraen-9-one | Ligand Info | |||||
| Structure Description | Crystal structure of PDE5A in complex with inhibitor L1 | PDB:7FAQ | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [6] |
| PDB Sequence |
TRELQSLAAA
546 VVPSAQTLKI556 TDFSFSDFEL566 SDLETALCTI576 RMFTDLNLVQ586 NFQMKHEVLC 596 RWILSVKKNY606 RKNVAYHNWR616 HAFNTAQCMF626 AALKAGKIQN636 KLTDLEILAL 646 LIAALSHDLD656 HRGVNNSIME682 HHHFDQCLMI692 LNSPGNQILS702 GLSIEEYKTT 712 LKIIKQAILA722 TDLALYIKRR732 GEFFELIRKN742 QFNLEDPHQK752 ELFLAMLMTA 762 CDLSAITKPW772 PIQQRIAELV782 ATEFFDQGNK812 IPSMQVGFID822 AICLQLYEAL 832 THVSEDCFPL842 LDGCRKNRQK852 WQALAEQ
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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 .2OI or .2OI2 or .2OI3 or :32OI;style chemicals stick;color identity;select .A:612 or .A:613 or .A:617 or .A:764 or .A:765 or .A:767 or .A:768 or .A:775 or .A:778 or .A:779 or .A:782 or .A:783 or .A:786 or .A:787 or .A:813 or .A:816 or .A:817 or .A:820; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 5-[Bis(fluoranyl)methoxy]-2-[(4-chlorophenyl)methyl]-10-(3-methoxypropyl)-3,10-diazatricyclo[6.4.1.0^{4,13}]trideca-1,4(13),5,7-tetraen-9-one | Ligand Info | |||||
| Structure Description | Crystal structure of PDE5A in complex with inhibitor L12 | PDB:7FAR | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [6] |
| PDB Sequence |
TRELQSLAAA
546 VVPSAQTLKI556 TDFSFSDFEL566 SDLETALCTI576 RMFTDLNLVQ586 NFQMKHEVLC 596 RWILSVKKNY606 RKNVAYHNWR616 HAFNTAQCMF626 AALKAGKIQN636 KLTDLEILAL 646 LIAALSHDLD656 HRGVNNSYIQ666 HSIMEHHHFD687 QCLMILNSPG697 NQILSGLSIE 707 EYKTTLKIIK717 QAILATDLAL727 YIKRRGEFFE737 LIRKNQFNLE747 DPHQKELFLA 757 MLMTACDLSA767 ITKPWPIQQR777 IAELVATEFF787 DQGNKIPSMQ817 VGFIDAICLQ 827 LYEALTHVSE837 DCFPLLDGCR847 KNRQKWQALA857 EQ
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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 .2VI or .2VI2 or .2VI3 or :32VI;style chemicals stick;color identity;select .A:612 or .A:613 or .A:617 or .A:654 or .A:725 or .A:764 or .A:765 or .A:767 or .A:768 or .A:775 or .A:778 or .A:779 or .A:782 or .A:783 or .A:786 or .A:787 or .A:813 or .A:816 or .A:817 or .A:820; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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TYR612
3.635
HIS613
2.695
HIS617
4.104
ASP654
4.175
LEU725
3.834
ASP764
3.441
LEU765
3.231
ALA767
3.711
ILE768
3.570
GLN775
2.813
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| Ligand Name: 5-Bromo-6-Ethyl-2-{5-[(4-Methylpiperazin-1-Yl)sulfonyl]-2-Propoxyphenyl}pyrimidin-4(3h)-One | Ligand Info | |||||
| Structure Description | Crystal structure of the PDE5A1 catalytic domain in complex with novel inhibitors | PDB:3SIE | ||||
| Method | X-ray diffraction | Resolution | 1.93 Å | Mutation | No | [7] |
| PDB Sequence |
RELQSLAAAV
547 VPSAQTLKIT557 DFSFSDFELS567 DLETALCTIR577 MFTDLNLVQN587 FQMKHEVLCR 597 WILSVKKNYR607 KNVAYHNWRH617 AFNTAQCMFA627 ALKAGKIQNK637 LTDLEILALL 647 IAALSHDLDH657 IMEHHHFDQC689 LMILNSPGNQ699 ILSGLSIEEY709 KTTLKIIKQA 719 ILATDLALYI729 KRRGEFFELI739 RKNQFNLEDP749 HQKELFLAML759 MTACDLSAIT 769 KPWPIQQRIA779 ELVATEFFDQ789 GDRERKEPTD803 LMNREKKNKI813 PSMQVGFIDA 823 ICLQLYEALT833 HVSEDCFPLL843 DGCRKNRQKW853 QALAEQQ
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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 .5BO or .5BO2 or .5BO3 or :35BO;style chemicals stick;color identity;select .A:612 or .A:613 or .A:680 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
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| Ligand Name: 5-Bromo-2-{5-[(4-Methylpiperazin-1-Yl)acetyl]-2-Propoxyphenyl}-6-(Propan-2-Yl)pyrimidin-4(3h)-One | Ligand Info | |||||
| Structure Description | Crystal structure of the PDE5A1 catalytic domain in complex with novel inhibitors | PDB:4I9Z | ||||
| Method | X-ray diffraction | Resolution | 2.08 Å | Mutation | No | [8] |
| PDB Sequence |
EETRELQSLA
544 AAVVPSAQTL554 KITDFSFSDF564 ELSDLETALC574 TIRMFTDLNL584 VQNFQMKHEV 594 LCRWILSVKK604 NYRKNVAYHN614 WRHAFNTAQC624 MFAALKAGKI634 QNKLTDLEIL 644 ALLIAALSHD654 LDHRGVNNSY664 LAQLYCHSIM681 EHHHFDQCLM691 ILNSPGNQIL 701 SGLSIEEYKT711 TLKIIKQAIL721 ATDLALYIKR731 RGEFFELIRK741 NQFNLEDPHQ 751 KELFLAMLMT761 ACDLSAITKP771 WPIQQRIAEL781 VATEFFDKNK812 IPSMQVGFID 822 AICLQLYEAL832 THVSEDCFPL842 LDGCRKNRQK852 WQALAE
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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 .5BA or .5BA2 or .5BA3 or :35BA;style chemicals stick;color identity;select .A:612 or .A:613 or .A:725 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:813 or .A:816 or .A:817 or .A:819 or .A:820 or .A:823 or .A:824; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 6-Ethyl-2-{5-[(4-Methylpiperazin-1-Yl)sulfonyl]-2-Propoxyphenyl}pyrimidin-4(3h)-One | Ligand Info | |||||
| Structure Description | Crystal structure of the PDE5A1 catalytic domain in complex with novel inhibitors | PDB:4OEX | ||||
| Method | X-ray diffraction | Resolution | 2.14 Å | Mutation | No | [9] |
| PDB Sequence |
MEETRELQSL
543 AAAVVPSAQT553 LKITDFSFSD563 FELSDLETAL573 CTIRMFTDLN583 LVQNFQMKHE 593 VLCRWILSVK603 KNYRKNVAYH613 NWRHAFNTAQ623 CMFAALKAGK633 IQNKLTDLEI 643 LALLIAALSH653 DLDHRGVNNS663 YIQRSIMEHH684 HFDQCLMILN694 SPGNQILSGL 704 SIEEYKTTLK714 IIKQAILATD724 LALYIKRRGE734 FFELIRKNQF744 NLEDPHQKEL 754 FLAMLMTACD764 LSAITKPWPI774 QQRIAELVAT784 EFFDQGKNKI813 PSMQVGFIDA 823 ICLQLYEALT833 HVSEDCFPLL843 DGCRKNRQKW853 QALAEQQ
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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 .5EO or .5EO2 or .5EO3 or :35EO;style chemicals stick;color identity;select .A:612 or .A:613 or .A:725 or .A:765 or .A:768 or .A:775 or .A:779 or .A:782 or .A:783 or .A:786 or .A:787 or .A:813 or .A:816 or .A:817 or .A:820 or .A:824; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: N-[3-(4,5-diethyl-6-oxo-1,6-dihydropyrimidin-2-yl)-4-propoxyphenyl]-2-(4-methylpiperazin-1-yl)acetamide | Ligand Info | |||||
| Structure Description | Crystal structure of PDE5A in complex with a novel inhibitor | PDB:6IWI | ||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | No | [10] |
| PDB Sequence |
ETRELQSLAA
545 AVVPSAQTLK555 ITDFSFSDFE565 LSDLETALCT575 IRMFTDLNLV585 QNFQMKHEVL 595 CRWILSVKKN605 YRKNVAYHNW615 RHAFNTAQCM625 FAALKAGKIQ635 NKLTDLEILA 645 LLIAALSHDL655 DHRGVNNHSI680 MEHHHFDQCL690 MILNSPGNQI700 LSGLSIEEYK 710 TTLKIIKQAI720 LATDLALYIK730 RRGEFFELIR740 KNQFNLEDPH750 QKELFLAMLM 760 TACDLSAITK770 PWPIQQRIAE780 LVATEFFDQK810 NKIPSMQVGF820 IDAICLQLYE 830 ALTHVSEDCF840 PLLDGCRKNR850 QKWQALAEQQ860
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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 .B0C or .B0C2 or .B0C3 or :3B0C;style chemicals stick;color identity;select .A:612 or .A:613 or .A:725 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:787 or .A:813 or .A:816 or .A:817 or .A:819 or .A:820 or .A:823 or .A:824; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 5-Bromo-2-{2-Ethoxy-5-[(4-Methylpiperazin-1-Yl)sulfonyl]phenyl}-6-Octylpyrimidin-4(3h)-One | Ligand Info | |||||
| Structure Description | Crystal structure of the PDE5A1 catalytic domain in complex with novel inhibitors | PDB:4IA0 | ||||
| Method | X-ray diffraction | Resolution | 2.17 Å | Mutation | No | [8] |
| PDB Sequence |
EETRELQSLA
544 AAVVPSAQTL554 KITDFSFSDF564 ELSDLETALC574 TIRMFTDLNL584 VQNFQMKHEV 594 LCRWILSVKK604 NYRKNVAYHN614 WRHAFNTAQC624 MFAALKAGKI634 QNKLTDLEIL 644 ALLIAALSHD654 LDHRGVNNSQ674 LYCHSIMEHH684 HFDQCLMILN694 SPGNQILSGL 704 SIEEYKTTLK714 IIKQAILATD724 LALYIKRRGE734 FFELIRKNQF744 NLEDPHQKEL 754 FLAMLMTACD764 LSAITKPWPI774 QQRIAELVAT784 EFFDNKIPSM816 QVGFIDAICL 826 QLYEALTHVS836 EDCFPLLDGC846 RKNRQKWQAL856 AE
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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 .5BB or .5BB2 or .5BB3 or :35BB;style chemicals stick;color identity;select .A:612 or .A:613 or .A:660 or .A:723 or .A:725 or .A:761 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:787 or .A:813 or .A:816 or .A:817 or .A:820 or .A:824; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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TYR612
3.613
HIS613
4.068
VAL660
4.996
THR723
3.152
LEU725
3.661
THR761
3.988
ASP764
3.116
LEU765
3.604
ALA767
4.780
ILE768
3.604
GLN775
4.396
|
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| Ligand Name: 5-Chloro-6-Ethyl-2-{5-[(4-Methylpiperazin-1-Yl)sulfonyl]-2-Propoxyphenyl}pyrimidin-4(3h)-One | Ligand Info | |||||
| Structure Description | Crystal structure of PDE5A in complex with its inhibitor | PDB:4G2W | ||||
| Method | X-ray diffraction | Resolution | 2.28 Å | Mutation | No | [11] |
| PDB Sequence |
TRELQSLAAA
546 VVPSAQTLKI556 TDFSFSDFEL566 SDLETALCTI576 RMFTDLNLVQ586 NFQMKHEVLC 596 RWILSVKKNY606 RKNVAYHNWR616 HAFNTAQCMF626 AALKAGKIQN636 KLTDLEILAL 646 LIAALSHDLD656 HRGVNNSSIM681 EHHHFDQCLM691 ILNSPGNQIL701 SGLSIEEYKT 711 TLKIIKQAIL721 ATDLALYIKR731 RGEFFELIRK741 NQFNLEDPHQ751 KELFLAMLMT 761 ACDLSAITKP771 WPIQQRIAEL781 VATEFFDQNK812 IPSMQVGFID822 AICLQLYEAL 832 THVSEDCFPL842 LDGCRKNRQK852 WQALAE
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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 .NI0 or .NI02 or .NI03 or :3NI0;style chemicals stick;color identity;select .A:612 or .A:613 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:787 or .A:813 or .A:816 or .A:817 or .A:820 or .A:824; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 2-{5-[(4-Methylpiperazin-1-Yl)sulfonyl]-2-Propoxyphenyl}-3,5,6,7-Tetrahydro-4h-Cyclopenta[d]pyrimidin-4-One | Ligand Info | |||||
| Structure Description | Crystal structure of PDE5A complexed with its inhibitor | PDB:4G2Y | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [11] |
| PDB Sequence |
MEETRELQSL
543 AAAVVPSAQT553 LKITDFSFSD563 FELSDLETAL573 CTIRMFTDLN583 LVQNFQMKHE 593 VLCRWILSVK603 KNYRKNVAYH613 NWRHAFNTAQ623 CMFAALKAGK633 IQNKLTDLEI 643 LALLIAALSH653 DLDHRGVNNS663 PLAQLYCHSI680 MEHHHFDQCL690 MILNSPGNQI 700 LSGLSIEEYK710 TTLKIIKQAI720 LATDLALYIK730 RRGEFFELIR740 KNQFNLEDPH 750 QKELFLAMLM760 TACDLSAITK770 PWPIQQRIAE780 LVATEFFDKN811 KIPSMQVGFI 821 DAICLQLYEA831 LTHVSEDCFP841 LLDGCRKNRQ851 KWQALAE
|
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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 .NI5 or .NI52 or .NI53 or :3NI5;style chemicals stick;color identity;select .A:612 or .A:725 or .A:764 or .A:765 or .A:767 or .A:768 or .A:775 or .A:778 or .A:779 or .A:782 or .A:783 or .A:786 or .A:787 or .A:813 or .A:816 or .A:817 or .A:820 or .A:824; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 6-Ethyl-5-Iodo-2-{5-[(4-Methylpiperazin-1-Yl)sulfonyl]-2-Propoxyphenyl}pyrimidin-4(3h)-One | Ligand Info | |||||
| Structure Description | Crystal structure of the PDE5A1 catalytic domain in complex with novel inhibitors | PDB:4OEW | ||||
| Method | X-ray diffraction | Resolution | 2.44 Å | Mutation | No | [9] |
| PDB Sequence |
TRELQSLAAA
546 VVPSAQTLKI556 TDFSFSDFEL566 SDLETALCTI576 RMFTDLNLVQ586 NFQMKHEVLC 596 RWILSVKKNY606 RKNVAYHNWR616 HAFNTAQCMF626 AALKAGKIQN636 KLTDLEILAL 646 LIAALSHDLD656 HRGVNNSIME682 HHHFDQCLMI692 LNSPGNQILS702 GLSIEEYKTT 712 LKIIKQAILA722 TDLALYIKRR732 GEFFELIRKN742 QFNLEDPHQK752 ELFLAMLMTA 762 CDLSAITKPW772 PIQQRIAELV782 ATEFFDQGKN811 KIPSMQVGFI821 DAICLQLYEA 831 LTHVSEDCFP841 LLDGCRKNRQ851 KWQALAEQQ
|
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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 .5IO or .5IO2 or .5IO3 or :35IO;style chemicals stick;color identity;select .A:612 or .A:613 or .A:660 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:787 or .A:813 or .A:816 or .A:817 or .A:820 or .A:824; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 5-Chloro-6-Ethyl-2-{5-[(4-Methylpiperazin-1-Yl)sulfonyl]-2-Propoxyphenyl}pyrimidin-4(3h)-One | Ligand Info | |||||
| Structure Description | Crystal structure of the PDE5A1 catalytic domain in complex with novel inhibitors | PDB:3SHZ | ||||
| Method | X-ray diffraction | Resolution | 2.45 Å | Mutation | No | [7] |
| PDB Sequence |
ETRELQSLAA
545 AVVPSAQTLK555 ITDFSFSDFE565 LSDLETALCT575 IRMFTDLNLV585 QNFQMKHEVL 595 CRWILSVKKN605 YRKNVAYHNW615 RHAFNTAQCM625 FAALKAGKIQ635 NKLTDLEILA 645 LLIAALSHDL655 DHRGVNNSYI665 QRSEHSIMEH683 HHFDQCLMIL693 NSPGNQILSG 703 LSIEEYKTTL713 KIIKQAILAT723 DLALYIKRRG733 EFFELIRKNQ743 FNLEDPHQKE 753 LFLAMLMTAC763 DLSAITKPWP773 IQQRIAELVA783 TEFFDQKNKI813 PSMQVGFIDA 823 ICLQLYEALT833 HVSEDCFPLL843 DGCRKNRQKW853 QALAEQQ
|
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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 .5CO or .5CO2 or .5CO3 or :35CO;style chemicals stick;color identity;select .A:612 or .A:613 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:787 or .A:813 or .A:816 or .A:817 or .A:820 or .A:824; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 6-Ethyl-5-Fluoro-2-{5-[(4-Methylpiperazin-1-Yl)sulfonyl]-2-Propoxyphenyl}pyrimidin-4(3h)-One | Ligand Info | |||||
| Structure Description | Crystal structure of the PDE5A1 catalytic domain in complex with novel inhibitors | PDB:3SHY | ||||
| Method | X-ray diffraction | Resolution | 2.65 Å | Mutation | No | [7] |
| PDB Sequence |
ETRELQSLAA
545 AVVPSAQTLK555 ITDFSFSDFE565 LSDLETALCT575 IRMFTDLNLV585 QNFQMKHEVL 595 CRWILSVKKN605 YRKNVAYHNW615 RHAFNTAQCM625 FAALKAGKIQ635 NKLTDLEILA 645 LLIAALSHDL655 DHRGVNNSYI665 QRSEHSIMEH683 HHFDQCLMIL693 NSPGNQILSG 703 LSIEEYKTTL713 KIIKQAILAT723 DLALYIKRRG733 EFFELIRKNQ743 FNLEDPHQKE 753 LFLAMLMTAC763 DLSAITKPWP773 IQQRIAELVA783 TEFFDQKKNK812 IPSMQVGFID 822 AICLQLYEAL832 THVSEDCFPL842 LDGCRKNRQK852 WQALAEQQ
|
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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 .5FO or .5FO2 or .5FO3 or :35FO;style chemicals stick;color identity;select .A:612 or .A:613 or .A:725 or .A:765 or .A:767 or .A:768 or .A:775 or .A:778 or .A:779 or .A:782 or .A:783 or .A:786 or .A:787 or .A:813 or .A:816 or .A:817 or .A:820 or .A:824; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 1-(5-Chloro-6-Methoxypyridin-3-Yl)-3-Methyl-N-(Methylsulfonyl)-1h-Indazole-5-Carboxamide | Ligand Info | |||||
| Structure Description | PDE5A for NaV1.7 | PDB:5JO3 | ||||
| Method | X-ray diffraction | Resolution | 1.49 Å | Mutation | No | [12] |
| PDB Sequence |
TRELQSLAAA
546 VVPSAQTLKI556 TDFSFSDFEL566 SDLETALCTI576 RMFTDLNLVQ586 NFQMKHEVLC 596 RWILSVKKNY606 RKNVAYHNWR616 HAFNTAQCMF626 AALKAGKIQN636 KLTDLEILAL 646 LIAALSHDLD656 HPGVSNQFLI666 NTNSELALMY676 NDESVLEHHH685 FDQCLMILNS 695 PGNQILSGLS705 IEEYKTTLKI715 IKQAILATDL725 ALYIKRRGEF735 FELIRKNQFN 745 LEDPHEKELF755 LAMLMTACDL765 SAITKPWPIQ775 QRIAELVATE785 FFDQGDRERK 795 ELNIEPTDLM805 NREKKNKIPS815 MQVGFIDAIC825 LQLYEALTHV835 SEDCFPLLDG 845 CRKNRQKWQA855 LAE
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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 .6LK or .6LK2 or .6LK3 or :36LK;style chemicals stick;color identity;select .B:612 or .B:725 or .B:764 or .B:765 or .B:766 or .B:767 or .B:768 or .B:775 or .B:778 or .B:779 or .B:782 or .B:786 or .B:804 or .B:816 or .B:817 or .B:820; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 5-[2-(But-3-EN-1-yloxy)-5-(1-hydroxyvinyl)pyridin-3-YL]-3-ethyl-2-(1-ethylazetidin-3-YL)-1,2,6,7A-tetrahydro-7H-pyrazolo[4,3-D]pyrimidin-7-one | Ligand Info | |||||
| Structure Description | Crystal structure of N2 substituted pyrazolo pyrimidinones - a flipped binding mode in PDE5 | PDB:2CHM | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | No | [13] |
| PDB Sequence |
TRELQSLAAA
546 VVPSAQTLKI556 TDFSFSDFEL566 SDLETALCTI576 RMFTDLNLVQ586 NFQMKHEVLC 596 RWILSVKKNY606 RKNVAYHNWR616 HAFNTAQCMF626 AALKAGKIQN636 KLTDLEILAL 646 LIAALSHDLD656 HPGVSNQFLI666 NTNSELALMY676 NDESVLEHHH685 FDQCLMILNS 695 PGNQILSGLS705 IEEYKTTLKI715 IKQAILATDL725 ALYIKRRGEF735 FELIRKNQFN 745 LEDPHEKELF755 LAMLMTACDL765 SAITKPWPIQ775 QRIAELVATE785 FFDQGDRERK 795 ELNIEPTDLM805 NREKKNKIPS815 MQVGFIDAIC825 LQLYEALTHV835 SEDCFPLLDG 845 CRKNRQKWQA855 LAE
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .3P4 or .3P42 or .3P43 or :33P4;style chemicals stick;color identity;select .A:612 or .A:725 or .A:729 or .A:764 or .A:765 or .A:766 or .A:767 or .A:768 or .A:775 or .A:778 or .A:779 or .A:782 or .A:783 or .A:786 or .A:787 or .A:804 or .A:813 or .A:816 or .A:817 or .A:820 or .A:824; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TYR612
3.941
LEU725
3.646
ILE729
4.217
ASP764
4.747
LEU765
3.303
SER766
4.969
ALA767
3.158
ILE768
3.047
GLN775
3.009
ILE778
4.712
ALA779
3.442
|
|||||
| Ligand Name: 5,7-Dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbutyl)-4-oxo-4H-chromen-3-YL 6-deoxy-alpha-L-mannopyranoside | Ligand Info | |||||
| Structure Description | Crystal structure of PDE5A1 in complex with icarisid II | PDB:2H44 | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [14] |
| 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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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .7CA or .7CA2 or .7CA3 or :37CA;style chemicals stick;color identity;select .A:612 or .A:613 or .A:617 or .A:661 or .A:663 or .A:664 or .A:665 or .A:668 or .A:723 or .A:725 or .A:764 or .A:765 or .A:767 or .A:768 or .A:775 or .A:778 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:820; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TYR612
3.375
HIS613
2.707
HIS617
4.511
ASN661
3.577
SER663
3.538
TYR664
3.394
ILE665
2.829
SER668
2.979
THR723
4.544
LEU725
3.649
ASP764
2.759
LEU765
3.683
ALA767
3.301
|
|||||
| Ligand Name: 7-(6-Methoxypyridin-3-Yl)-4-{[2-(Propan-2-Yloxy)ethyl]amino}-1-(2-Propoxyethyl)pyrido[4,3-D]pyrimidin-2(1h)-One | Ligand Info | |||||
| Structure Description | A novel series of potent and selective PDE5 inhibitor2 | PDB:3TGG | ||||
| Method | X-ray diffraction | Resolution | 1.91 Å | Mutation | Yes | [15] |
| PDB Sequence |
ETRELQSLAA
545 AVVPSAQTLK555 ITDFSFSDFE565 LSDLETALCT575 IRMFTDLNLV585 QNFQMKHEVL 595 CRWILSVKKN605 YRKNVAYHNW615 RHAFNTAQCM625 FAALKAGKIQ635 NKLTDLEILA 645 LLIAALSHDL655 DHPGVSNQFL665 INTNSELALM675 YNDESVLEHH684 HFDQCLMILN 694 SPGNQILSGL704 SIEEYKTTLK714 IIKQAILATD724 LALYIKRRGE734 FFELIRKNQF 744 NLEDPHEKEL754 FLAMLMTACD764 LSAITKPWPI774 QQRIAELVAT784 EFFDQGDRER 794 KELNIEPTDL804 MNREKKNKIP814 SMQVGFIDAI824 CLQLYEALTH834 VSEDCFPLLD 844 GCRKNRQKWQ854 ALAE
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .0H3 or .0H32 or .0H33 or :30H3;style chemicals stick;color identity;select .A:612 or .A:725 or .A:729 or .A:764 or .A:765 or .A:767 or .A:768 or .A:775 or .A:778 or .A:779 or .A:780 or .A:782 or .A:783 or .A:786 or .A:804 or .A:812 or .A:813 or .A:816 or .A:817 or .A:820 or .A:824; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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TYR612
3.273
LEU725
3.589
ILE729
2.799
ASP764
4.476
LEU765
3.286
ALA767
2.909
ILE768
3.296
GLN775
2.618
ILE778
3.383
ALA779
2.704
GLU780
4.775
|
|||||
| Ligand Name: 7-(6-Methoxypyridin-3-Yl)-3-{[2-(Morpholin-4-Yl)ethyl]amino}-1-(2-Propoxyethyl)pyrido[3,4-B]pyrazin-2(1h)-One | Ligand Info | |||||
| Structure Description | A novel series of potent and selective PDE5 inhibitor1 | PDB:3TGE | ||||
| Method | X-ray diffraction | Resolution | 1.96 Å | Mutation | No | [15] |
| PDB Sequence |
ETRELQSLAA
545 AVVPSAQTLK555 ITDFSFSDFE565 LSDLETALCT575 IRMFTDLNLV585 QNFQMKHEVL 595 CRWILSVKKN605 YRKNVAYHNW615 RHAFNTAQCM625 FAALKAGKIQ635 NKLTDLEILA 645 LLIAALSHDL655 DHPGVSNQFL665 INTNSELALM675 YNDESVLEHH684 HFDQCLMILN 694 SPGNQILSGL704 SIEEYKTTLK714 IIKQAILATD724 LALYIKRRGE734 FFELIRKNQF 744 NLEDPHEKEL754 FLAMLMTACD764 LSAITKPWPI774 QQRIAELVAT784 EFFDQGDRER 794 KELNIEPTDL804 MNREKKNKIP814 SMQVGFIDAI824 CLQLYEALTH834 VSEDCFPLLD 844 GCRKNRQKWQ854 ALAE
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .TGE or .TGE2 or .TGE3 or :3TGE;style chemicals stick;color identity;select .A:612 or .A:725 or .A:726 or .A:729 or .A:765 or .A:767 or .A:768 or .A:775 or .A:778 or .A:779 or .A:780 or .A:782 or .A:783 or .A:786 or .A:804 or .A:813 or .A:816 or .A:817 or .A:820 or .A:824 or .A:853; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TYR612
3.998
LEU725
3.518
ALA726
4.939
ILE729
2.209
LEU765
3.638
ALA767
2.743
ILE768
3.142
GLN775
2.675
ILE778
3.284
ALA779
2.608
GLU780
4.662
|
|||||
| Ligand Name: 3-(4-Hydroxybenzyl)-1-(Thiophen-2-Yl)chromeno[2,3-C]pyrrol-9(2h)-One | Ligand Info | |||||
| Structure Description | Crystal structure of PDE5 in complex with inhibitor 5R | PDB:4MD6 | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [16] |
| PDB Sequence |
EETRELQSLA
544 AAVVPSAQTL554 KITDFSFSDF564 ELSDLETALC574 TIRMFTDLNL584 VQNFQMKHEV 594 LCRWILSVKK604 NYRKNVAYHN614 WRHAFNTAQC624 MFAALKAGKI634 QNKLTDLEIL 644 ALLIAALSHD654 LDHRGVNNSY664 IQCHSIMEHH684 HFDQCLMILN694 SPGNQILSGL 704 SIEEYKTTLK714 IIKQAILATD724 LALYIKRRGE734 FFELIRKNQF744 NLEDPHQKEL 754 FLAMLMTACD764 LSAITKPWPI774 QQRIAELVAT784 EFFDQGEKKN811 KIPSMQVGFI 821 DAICLQLYEA831 LTHVSEDCFP841 LLDGCRKNRQ851 KWQALAEQQ
|
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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 .24E or .24E2 or .24E3 or :324E;style chemicals stick;color identity;select .A:612 or .A:725 or .A:765 or .A:767 or .A:768 or .A:775 or .A:778 or .A:779 or .A:782 or .A:783 or .A:786 or .A:787 or .A:813 or .A:816 or .A:817 or .A:820; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 3-[(2H-1,3-benzodioxol-5-yl)methyl]-8-fluoro-1-(1,3-thiazol-2-yl)[1]benzopyrano[2,3-c]pyrrol-9(2H)-one | Ligand Info | |||||
| Structure Description | Crystal structure of PDE5 in complex with inhibitor LW1634 | PDB:5ZZ2 | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [17] |
| PDB Sequence |
EETRELQSLA
544 AAVVPSAQTL554 KITDFSFSDF564 ELSDLETALC574 TIRMFTDLNL584 VQNFQMKHEV 594 LCRWILSVKK604 NYRKNVAYHN614 WRHAFNTAQC624 MFAALKAGKI634 QNKLTDLEIL 644 ALLIAALSHD654 LDHRGVNNSY664 IQCHSIMEHH684 HFDQCLMILN694 SPGNQILSGL 704 SIEEYKTTLK714 IIKQAILATD724 LALYIKRRGE734 FFELIRKNQF744 NLEDPHQKEL 754 FLAMLMTACD764 LSAITKPWPI774 QQRIAELVAT784 EFFDQGEKKN811 KIPSMQVGFI 821 DAICLQLYEA831 LTHVSEDCFP841 LLDGCRKNRQ851 KWQALAEQQ
|
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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 .9M0 or .9M02 or .9M03 or :39M0;style chemicals stick;color identity;select .A:612 or .A:725 or .A:765 or .A:767 or .A:768 or .A:775 or .A:778 or .A:779 or .A:782 or .A:783 or .A:786 or .A:787 or .A:813 or .A:816 or .A:817 or .A:820; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 3-[(2H-1,3-benzodioxol-5-yl)methyl]-8-fluoro-6-{[2-(4-methylpiperazin-1-yl)ethyl]amino}-1-(1,3-thiazol-2-yl)[1]benzopyrano[2,3-c]pyrrol-9(2H)-one | Ligand Info | |||||
| Structure Description | Crystal structure of PDE5 in complex with inhibitor LW1805 | PDB:6ACB | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [17] |
| 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 EFFDQEKKNK 812 IPSMQVGFID822 AICLQLYEAL832 THVSEDCFPL842 LDGCRKNRQK852 WQALAEQQ |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .9T9 or .9T92 or .9T93 or :39T9;style chemicals stick;color identity;select .A:612 or .A:660 or .A:676 or .A:725 or .A:765 or .A:767 or .A:768 or .A:775 or .A:778 or .A:782 or .A:783 or .A:786 or .A:787 or .A:813 or .A:816 or .A:817 or .A:820; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 6-(6-methoxypyridin-3-yl)-2-[(2-morpholin-4-ylethyl)amino]-4-(2-propoxyethyl)pyrido[2,3-b]pyrazin-3(4H)-one | Ligand Info | |||||
| Structure Description | Investigation of Aminopyridiopyrazinones as PDE5 Inhibitors: Evaluation of Modifications to the Central Ring System. | PDB:3HC8 | ||||
| Method | X-ray diffraction | Resolution | 1.79 Å | Mutation | No | [18] |
| PDB Sequence |
ETRELQSLAA
545 AVVPSAQTLK555 ITDFSFSDFE565 LSDLETALCT575 IRMFTDLNLV585 QNFQMKHEVL 595 CRWILSVKKN605 YRKNVAYHNW615 RHAFNTAQCM625 FAALKAGKIQ635 NKLTDLEILA 645 LLIAALSHDL655 DHPGVSNQFL665 INTNSELALM675 YNDESVLEHH684 HFDQCLMILN 694 SPGNQILSGL704 SIEEYKTTLK714 IIKQAILATD724 LALYIKRRGE734 FFELIRKNQF 744 NLEDPHEKEL754 FLAMLMTACD764 LSAITKPWPI774 QQRIAELVAT784 EFFDQGDRER 794 KELNIEPTDL804 MNREKKNKIP814 SMQVGFIDAI824 CLQLYEALTH834 VSEDCFPLLD 844 GCRKNRQKWQ854 ALAE
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .PD4 or .PD42 or .PD43 or :3PD4;style chemicals stick;color identity;select .A:612 or .A:663 or .A:725 or .A:726 or .A:729 or .A:765 or .A:767 or .A:768 or .A:775 or .A:778 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:820; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 5-Amino-1-butyl-7-phenyl-1,6-naphthyridin-4(1H)-one | Ligand Info | |||||
| Structure Description | Identification, Synthesis, and SAR of Amino Substituted Pyrido[3,2b]pryaziones as Potent and Selective PDE5 Inhibitors | PDB:3HDZ | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [19] |
| PDB Sequence |
TRELQSLAAA
546 VVPSAQTLKI556 TDFSFSDFEL566 SDLETALCTI576 RMFTDLNLVQ586 NFQMKHEVLC 596 RWILSVKKNY606 RKNVAYHNWR616 HAFNTAQCMF626 AALKAGKIQN636 KLTDLEILAL 646 LIAALSHDLD656 HPGVSNQFLI666 NTNSELALMY676 NDESVLEHHH685 FDQCLMILNS 695 PGNQILSGLS705 IEEYKTTLKI715 IKQAILATDL725 ALYIKRRGEF735 FELIRKNQFN 745 LEDPHEKELF755 LAMLMTACDL765 SAITKPWPIQ775 QRIAELVATE785 FFDQGDRERK 795 ELNIEPTDLM805 NREKKNKIPS815 MQVGFIDAIC825 LQLYEALTHV835 SEDCFPLLDG 845 CRKNRQKWQA855 LAE
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| Ligand Name: (13bS)-4,9-dimethoxy-14-methyl-8,13,13b,14-tetrahydroindolo[2',3':3,4]pyrido[2,1-b]quinazolin-5(7H)-one | Ligand Info | |||||
| Structure Description | crystal structure of PDE5 in complex with a non-competitive inhibitor | PDB:6VBI | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [20] |
| 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 EFFDKNKIPS 815 MQVGFIDAIC825 LQLYEALTHV835 SEDCFPLLDG845 CRKNRQKWQA855 LAEQ |
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structural basis for the activity of drugs that inhibit phosphodiesterases. Structure. 2004 Dec;12(12):2233-47. | ||||
| REF 2 | A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases. Mol Cell. 2004 Jul 23;15(2):279-86. | ||||
| REF 3 | Structure of Human Phosphodiesterase 5A1 Complexed with Avanafil Reveals Molecular Basis of Isoform Selectivity and Guidelines for Targeting Alpha-Helix Backbone Oxygen by Halogen Bonding. J Med Chem. 2020 Aug 13;63(15):8485-8494. | ||||
| REF 4 | Crystal structures of phosphodiesterases 4 and 5 in complex with inhibitor 3-isobutyl-1-methylxanthine suggest a conformation determinant of inhibitor selectivity. J Biol Chem. 2004 Mar 26;279(13):13095-101. | ||||
| REF 5 | An insight into the pharmacophores of phosphodiesterase-5 inhibitors from synthetic and crystal structural studies. Biochem Pharmacol. 2008 May 1;75(9):1717-28. | ||||
| REF 6 | Free energy perturbation (FEP)-guided scaffold hopping. Acta Pharm Sin B. 2022 Mar;12(3):1351-1362. | ||||
| REF 7 | Utilization of halogen bond in lead optimization: a case study of rational design of potent phosphodiesterase type 5 (PDE5) inhibitors. J Med Chem. 2011 Aug 11;54(15):5607-11. | ||||
| REF 8 | Exploration of the 5-bromopyrimidin-4(3H)-ones as potent inhibitors of PDE5. Bioorg Med Chem Lett. 2013 Sep 1;23(17):4944-7. | ||||
| REF 9 | Thermodynamic and structural characterization of halogen bonding in protein-ligand interactions: a case study of PDE5 and its inhibitors. J Med Chem. 2014 Apr 24;57(8):3588-93. | ||||
| REF 10 | Pharmacokinetics-Driven Optimization of 4(3 H)-Pyrimidinones as Phosphodiesterase Type 5 Inhibitors Leading to TPN171, a Clinical Candidate for the Treatment of Pulmonary Arterial Hypertension. J Med Chem. 2019 May 23;62(10):4979-4990. | ||||
| REF 11 | Design, synthesis, and pharmacological evaluation of monocyclic pyrimidinones as novel inhibitors of PDE5. J Med Chem. 2012 Dec 13;55(23):10540-50. | ||||
| REF 12 | PDE5A for NaV1.7 | ||||
| REF 13 | A novel series of potent and selective PDE5 inhibitors with potential for high and dose-independent oral bioavailability. J Med Chem. 2006 Jun 15;49(12):3581-94. | ||||
| REF 14 | Multiple conformations of phosphodiesterase-5: implications for enzyme function and drug development. J Biol Chem. 2006 Jul 28;281(30):21469-21479. | ||||
| REF 15 | Investigation of the pyrazinones as PDE5 inhibitors: evaluation of regioisomeric projections into the solvent region. Bioorg Med Chem Lett. 2011 Nov 1;21(21):6348-52. | ||||
| REF 16 | Discovery of 3-(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one as a phosphodiesterase-5 inhibitor and its complex crystal structure. Biochem Pharmacol. 2014 May 1;89(1):86-98. | ||||
| REF 17 | Optimization of Chromeno[2,3- c]pyrrol-9(2 H)-ones as Highly Potent, Selective, and Orally Bioavailable PDE5 Inhibitors: Structure-Activity Relationship, X-ray Crystal Structure, and Pharmacodynamic Effect on Pulmonary Arterial Hypertension. J Med Chem. 2018 Sep 27;61(18):8468-8473. | ||||
| REF 18 | Investigation of aminopyridiopyrazinones as PDE5 inhibitors: Evaluation of modifications to the central ring system. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4092-6. | ||||
| REF 19 | Identification, synthesis and SAR of amino substituted pyrido[3,2b]pyrazinones as potent and selective PDE5 inhibitors. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4088-91. | ||||
| REF 20 | Identification of a novel allosteric pocket and its regulation mechanism | ||||
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