Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T25265 | Target Info | |||
| Target Name | Enhancer of zeste homolog 2 (EZH2) | ||||
| Synonyms | Lysine Nmethyltransferase 6; Lysine N-methyltransferase 6; KMT6; Histonelysine Nmethyltransferase EZH2; Histone-lysine N-methyltransferase EZH2; EZH2; ENX1; ENX-1 | ||||
| Target Type | Successful Target | ||||
| Gene Name | EZH2 | ||||
| Biochemical Class | Methyltransferase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: GSK2816126 | Ligand Info | |||||
| Structure Description | Human Polycomb Repressive Complex 2 in complex with GSK126 inhibitor | PDB:5WG6 | ||||
| Method | X-ray diffraction | Resolution | 3.90 Å | Mutation | No | [1] |
| PDB Sequence |
RFRRADEVKS
40 MFSSNRQKIL50 ERTEILNQEW60 KQRRIQPVHI70 LTSVRECSVT86 SDLDFPTQVI 96 PLKTLNAVAS106 VPIMYSWSPL116 QQNFMVEDTP262 NIDGPNAKSV272 QREQSLHSFH 282 TLFCRRCFKY292 DCFLHPFHAT302 PNTYKRWSGA435 EASMFRVLIG445 TYYDNFCAIA 455 RLIGTKTCRQ465 VYEFRVKVYN519 YQPCDHPRQP529 CDSSCPCVIA539 QNFCEKFCQC 549 SSECQNRFPG559 CRCKAQCNTK569 QCPCYLAVRE579 CDPDLCLTCG589 AADHRDSKNV 599 SCKNCSIQRG609 SKKHLLLAPS619 DVAGWGIFIK629 DPVQKNEFIS639 EYCGEIISQD 649 EADRRGKVYD659 KYMCSFLFNL669 NNDFVVDATR679 KGNKIRFANH689 SVNPNCYAKV 699 MMVNGDHRIG709 IFAKRAIQTG719 EELFFDYRYS729 QNRLYFHSDT2570 CLPLRPQEME 2580 VDSEDEKDPE2590 WLREKTITQI2600 EEFSDVNEGE2610 KEVMKLWNLH2620 VMKHGFIADN 2630 QMNHACMLFV2640 ENYGQKIIKK2650 NLCRNFMLHL2660 VSMHDFNLIS2670 IMSIDKAVTK 2680 LREMQQK
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| Ligand Name: N-Trimethyllysine | Ligand Info | |||||
| Structure Description | Structure of Human Polycomb Repressive Complex 2 (PRC2) with inhibitor | PDB:5LS6 | ||||
| Method | X-ray diffraction | Resolution | 3.47 Å | Mutation | No | [2] |
| PDB Sequence |
KGPVCWRKRV
19 KSEYMRLRQL29 KRFRRADEVK39 SMFSSNRQKI49 LERTEILNQE59 WKQRRIQPVH 69 ILTSVSSLRG79 TRECSVTSDL89 DFPTQVIPLK99 TLNAVASVPI109 MYSWSPLQQN 119 FMVEDETVLH129 NIPYMGDEVL139 DQDGTFIEEL149 IKNYDGKVHG159 DRECGFINDE 169 IFVELVNALG179 QYNESRPPRS220 DKIFEAISSM230 FPDKGTAEEL240 KEKYKELTQP 257 PECTPNIDGP267 NAKSVQREQS277 LHSFHTLFCR287 RCFKYDCFLH297 PFHATPNTYK 307 RKNTETALDN317 KPCGPQCYQH327 LEGAKEFAAA337 LTAERIKTPN423 IEPPENVEWS 433 GAEASMFRVL443 IGTYYDNFCA453 IARLIGTKTC463 RQVYEFRVKE473 SSIIAPAHVY 518 NYQPCDHPRQ528 PCDSSCPCVI538 AQNFCEKFCQ548 CSSECQNRFP558 GCRCKAQCNT 568 KQCPCYLAVR578 ECDPDLCLTC588 GAADHWDSKN598 VSCKNCSIQR608 GSKKHLLLAP 618 SDVAGWGIFI628 KDPVQKNEFI638 SEYCGEIISQ648 DEADRRGKVY658 DKYMCSFLFN 668 LNNDFVVDAT678 RKGNKIRFAN688 HSVNPNCYAK698 VMMVNGDHRI708 GIFAKRAIQT 718 GEELFFDYRY728
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| Ligand Name: 5,8-Dichloro-2-[(4-Ethyl-6-Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)methyl]-7-({1-[(2r)-2-Hydroxypropanoyl]piperidin-4-Yl}oxy)-3,4-Dihydroisoquinolin-1(2h)-One | Ligand Info | |||||
| Structure Description | Structure of the primary oncogenic mutant Y641N Hs/AcPRC2 in complex with a pyridone inhibitor | PDB:5IJ8 | ||||
| Method | X-ray diffraction | Resolution | 2.99 Å | Mutation | Yes | [3] |
| PDB Sequence |
EKGPICWRKR
18 VKSEYMRLRQ28 LKRFRRADEV38 KSMFNSNRQK48 IQERTEILNQ58 EWKQRRIQPV 68 HIMRECSVTS87 DLDFPKQVIP97 LKTLNAVASV107 PIMYSWSPLQ117 QNFMVEDIND 168 EIFVELVNAL178 GQLDRRDEKP219 SDKIFEAISS229 MFPDKGTAEE239 LKEKYKECTP 262 NIDGPNAKSV272 QREQSLHSFH282 TLFCRRCFKY292 DCFLHPFHAT302 PNTYKRWSGA 435 EASMFRVLIG445 TYYDNFCAIA455 RLIGTKTCRQ465 VYEFRVKVYN519 YQPCDHPRQP 529 CDNSCPCVIA539 QNFCEKFCQC549 SSECQNRFPG559 CRCKAQCNTK569 QCPCYLAVRE 579 CDPDLCLTCG589 AADHWDSKNV599 SCKNCSIQRG609 SKKHLLLAPS619 DVAGWGIFIK 629 DPVQKNEFIS639 ENCGEIISQD649 EADRRGKVYD659 KYMCSFLFNL669 NNDFVVDATR 679 KGNKIRFANH689 SVNPNCYAKV699 MMVNGDHRIG709 IFAKRAIQTG719 EELFFDYRYS 729 QADA
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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 .6BN or .6BN2 or .6BN3 or :36BN;style chemicals stick;color identity;select .A:109 or .A:110 or .A:111 or .A:623 or .A:624 or .A:657 or .A:658 or .A:661 or .A:663 or .A:665 or .A:677 or .A:678 or .A:685 or .A:686 or .A:687 or .A:688 or .A:726; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 1-[(1~{R})-1-[1-[2,2-bis(fluoranyl)propyl]piperidin-4-yl]ethyl]-~{N}-[(4-methoxy-6-methyl-2-oxidanylidene-3~{H}-pyridin-3-yl)methyl]-2-methyl-indole-3-carboxamide | Ligand Info | |||||
| Structure Description | Structure of Human Polycomb Repressive Complex 2 (PRC2) with inhibitor | PDB:5LS6 | ||||
| Method | X-ray diffraction | Resolution | 3.47 Å | Mutation | No | [2] |
| PDB Sequence |
KGPVCWRKRV
19 KSEYMRLRQL29 KRFRRADEVK39 SMFSSNRQKI49 LERTEILNQE59 WKQRRIQPVH 69 ILTSVSSLRG79 TRECSVTSDL89 DFPTQVIPLK99 TLNAVASVPI109 MYSWSPLQQN 119 FMVEDETVLH129 NIPYMGDEVL139 DQDGTFIEEL149 IKNYDGKVHG159 DRECGFINDE 169 IFVELVNALG179 QYNESRPPRS220 DKIFEAISSM230 FPDKGTAEEL240 KEKYKELTQP 257 PECTPNIDGP267 NAKSVQREQS277 LHSFHTLFCR287 RCFKYDCFLH297 PFHATPNTYK 307 RKNTETALDN317 KPCGPQCYQH327 LEGAKEFAAA337 LTAERIKTPN423 IEPPENVEWS 433 GAEASMFRVL443 IGTYYDNFCA453 IARLIGTKTC463 RQVYEFRVKE473 SSIIAPAHVY 518 NYQPCDHPRQ528 PCDSSCPCVI538 AQNFCEKFCQ548 CSSECQNRFP558 GCRCKAQCNT 568 KQCPCYLAVR578 ECDPDLCLTC588 GAADHWDSKN598 VSCKNCSIQR608 GSKKHLLLAP 618 SDVAGWGIFI628 KDPVQKNEFI638 SEYCGEIISQ648 DEADRRGKVY658 DKYMCSFLFN 668 LNNDFVVDAT678 RKGNKIRFAN688 HSVNPNCYAK698 VMMVNGDHRI708 GIFAKRAIQT 718 GEELFFDYRY728
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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 .74D or .74D2 or .74D3 or :374D;style chemicals stick;color identity;select .A:109 or .A:110 or .A:111 or .A:130 or .A:132 or .A:622 or .A:623 or .A:624 or .A:625 or .A:657 or .A:658 or .A:661 or .A:663 or .A:665 or .A:678 or .A:685 or .A:686 or .A:687 or .A:688; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | An Evolutionarily Conserved Structural Platform for PRC2 Inhibition by a Class of Ezh2 Inhibitors. Sci Rep. 2018 Jun 14;8(1):9092. | ||||
| REF 2 | Identification of (R)-N-((4-Methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide (CPI-1205), a Potent and Selective Inhibitor of Histone Methyltransferase EZH2, Suitable for Phase I Clinical Trials for B-Cell Lymphomas. J Med Chem. 2016 Nov 10;59(21):9928-9941. | ||||
| REF 3 | Polycomb repressive complex 2 structure with inhibitor reveals a mechanism of activation and drug resistance. Nat Commun. 2016 Apr 28;7:11384. | ||||
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