Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T88304 | Target Info | |||
| Target Name | DNA [cytosine-5]-methyltransferase 1 (DNMT1) | ||||
| Synonyms | MCMT; M.HsaI; Dnmt1; DNMT; DNA methyltransferase HsaI; DNA MTase HsaI; DNA (cytosine5)methyltransferase 1; DNA (cytosine-5)-methyltransferase 1; CXXCtype zinc finger protein 9; CXXC9; CXXC-type zinc finger protein 9; AIM | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | DNMT1 | ||||
| Biochemical Class | Methyltransferase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Deoxy-5-methylcytidylic acid | Ligand Info | |||
| Canonical SMILES | CC1=CN(C(=O)N=C1N)C2CC(C(O2)COP(=O)(O)O)O | ||||
| InChI | 1S/C10H16N3O7P/c1-5-3-13(10(15)12-9(5)11)8-2-6(14)7(20-8)4-19-21(16,17)18/h3,6-8,14H,2,4H2,1H3,(H2,11,12,15)(H2,16,17,18)/t6-,7+,8+/m0/s1 | ||||
| InChIKey | RGDVNLHBCKWZDA-XLPZGREQSA-N | ||||
| PubChem Compound ID | 102276 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6X9J Human DNMT1(729-1600) Bound to Zebularine-Containing 12mer dsDNA and Inhibitor GSK3830052 | ||||||
| Method | X-ray diffraction | Resolution | 1.79 Å | Mutation | No | [1] |
| PDB Sequence |
NRISWVGEAV
738 KTDGKKSYYK748 KVCIDAETLE758 VGDCVSVIPD768 DSSKPLYLAR778 VTALWEDSSN 788 GQMFHAHWFC798 AGTDTVLGAT808 SDPLELFLVD818 ECEDMQLSYI828 HSKVKVIYKA 838 PSENWAMEGG848 MDPESLLEGD858 DGKTYFYQLW868 YDQDYARFES878 PPKTQPTEDN 888 KFKFCVSCAR898 LAEMRQKEIP908 RVLEQLEDLD918 SRVLYYSATK928 NGILYRVGDG 938 VYLPPEAFTF948 NIKLSSPVKR958 PRKEPVDEDL968 YPEHYRKYSD978 YIKGSNLDAP 988 EPYRIGRIKE998 IFCPKKSNGR1008 PNETDIKIRV1018 NKFYRPENTH1028 KSTPASYHAD 1038 INLLYWSDEE1048 AVVDFKAVQG1058 RCTVEYGEDL1068 PECVQVYSMG1078 GPNRFYFLEA 1088 YNAKSKSFED1098 PPNHARKLPK1138 LRTLDVFSGC1148 GGLSEGFHQA1158 GISDTLWAIE 1168 MWDPAAQAFR1178 LNNPGSTVFT1188 EDCNILLKLV1198 MAGETTNSRG1208 QRLPQKGDVE 1218 MLCGGPPCQG1228 FSGMNRFNSR1238 TYSKFKNSLV1248 VSFLSYCDYY1258 RPRFFLLENV 1268 RNFVSFKRSM1278 VLKLTLRCLV1288 RMGYQCTFGV1298 LQAGQYGVAQ1308 TRRRAIILAA 1318 APGEKLPLFP1328 EPLHVFAPRA1338 CQLSVVVDDK1348 KFVSNITRLS1358 SGPFRTITVR 1368 DTMSDLPEVR1378 NGASALEISY1388 NGEPQSWFQR1398 QLRGAQYQPI1408 LRDHICKDMS 1418 ALVAARMRHI1428 PLAPGSDWRD1438 LPNIEVRLSD1448 GTMARKLRYT1458 HHDRKNGRSS 1468 SGALRGVCSC1478 VEAGKACDPA1488 ARQFNTLIPW1498 CLPHTGNRHN1508 HWAGLYGRLE 1518 WDGFFSTTVT1528 NPEPMGKQGR1538 VLHPEQHRVV1548 SVRECARSQG1558 FPDTYRLFGN 1568 ILDKHRQVGN1578 AVPPPLAKAI1588 GLEIKLCMLA1598 KA
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| PDB ID: 7SFC Human DNMT1(729-1600) Bound to Zebularine-Containing 12mer dsDNA and Inhibitor GSK3735967A | ||||||
| Method | X-ray diffraction | Resolution | 1.97 Å | Mutation | No | [2] |
| PDB Sequence |
RISWVGEAVK
739 TDGKKSYYKK749 VCIDAETLEV759 GDCVSVIPDD769 SSKPLYLARV779 TALWEDSSNG 789 QMFHAHWFCA799 GTDTVLGATS809 DPLELFLVDE819 CEDMQLSYIH829 SKVKVIYKAP 839 SENWAMEGGM849 DPESLLEGDD859 GKTYFYQLWY869 DQDYARFESP879 PKTQPTEDNK 889 FKFCVSCARL899 AEMRQKEIPR909 VLEQLEDLDS919 RVLYYSATKN929 GILYRVGDGV 939 YLPPEAFTFN949 IKLSSPVKRP959 RKEPVDEDLY969 PEHYRKYSDY979 IKGSNLDAPE 989 PYRIGRIKEI999 FCPKKSNGRP1009 NETDIKIRVN1019 KFYRPENTHK1029 STPASYHADI 1039 NLLYWSDEEA1049 VVDFKAVQGR1059 CTVEYGEDLP1069 ECVQVYSMGG1079 PNRFYFLEAY 1089 NAKSKSFEDP1099 PNHARSKLPK1138 LRTLDVFSGC1148 GGLSEGFHQA1158 GISDTLWAIE 1168 MWDPAAQAFR1178 LNNPGSTVFT1188 EDCNILLKLV1198 MAGETTNSRG1208 QRLPQKGDVE 1218 MLCGGPPCQG1228 FSGMNRFNSR1238 TYSKFKNSLV1248 VSFLSYCDYY1258 RPRFFLLENV 1268 RNFVSFKRSM1278 VLKLTLRCLV1288 RMGYQCTFGV1298 LQAGQYGVAQ1308 TRRRAIILAA 1318 APGEKLPLFP1328 EPLHVFAPRA1338 CQLSVVVDDK1348 KFVSNITRLS1358 SGPFRTITVR 1368 DTMSDLPEVR1378 NGASALEISY1388 NGEPQSWFQR1398 QLRGAQYQPI1408 LRDHICKDMS 1418 ALVAARMRHI1428 PLAPGSDWRD1438 LPNIEVRLSD1448 GTMARKLRYT1458 HHDRKNGRSS 1468 SGALRGVCSC1478 VEAGKACDPA1488 ARQFNTLIPW1498 CLPHTGNRHN1508 HWAGLYGRLE 1518 WDGFFSTTVT1528 NPEPMGKQGR1538 VLHPEQHRVV1548 SVRECARSQG1558 FPDTYRLFGN 1568 ILDKHRQVGN1578 AVPPPLAKAI1588 GLEIKLCMLA1598 KA
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| PDB ID: 7SFF Human DNMT1(729-1600) Bound to Zebularine-Containing 12mer dsDNA and Inhibitor GSK3852279B | ||||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [2] |
| PDB Sequence |
RISWVGEAVK
739 TDGKKSYYKK749 VCIDAETLEV759 GDCVSVIPDD769 SSKPLYLARV779 TALWEDSSNG 789 QMFHAHWFCA799 GTDTVLGATS809 DPLELFLVDE819 CEDMQLSYIH829 SKVKVIYKAP 839 SENWAMEGGM849 DPESLLEGDD859 GKTYFYQLWY869 DQDYARFESP879 PKTQPTEDNK 889 FKFCVSCARL899 AEMRQKEIPR909 VLEQLEDLDS919 RVLYYSATKN929 GILYRVGDGV 939 YLPPEAFTFN949 IKLSSPVKRP959 RKEPVDEDLY969 PEHYRKYSDY979 IKGSNLDAPE 989 PYRIGRIKEI999 FCPKKSNGRP1009 NETDIKIRVN1019 KFYRPENTHK1029 STPASYHADI 1039 NLLYWSDEEA1049 VVDFKAVQGR1059 CTVEYGEDLP1069 ECVQVYSMGG1079 PNRFYFLEAY 1089 NAKSKSFEDP1099 PNHARSKLPK1138 LRTLDVFSGC1148 GGLSEGFHQA1158 GISDTLWAIE 1168 MWDPAAQAFR1178 LNNPGSTVFT1188 EDCNILLKLV1198 MAGETTNSRG1208 QRLPQKGDVE 1218 MLCGGPPCQG1228 FSGMNRFNSR1238 TYSKFKNSLV1248 VSFLSYCDYY1258 RPRFFLLENV 1268 RNFVSFKRSM1278 VLKLTLRCLV1288 RMGYQCTFGV1298 LQAGQYGVAQ1308 TRRRAIILAA 1318 APGEKLPLFP1328 EPLHVFAPRA1338 CQLSVVVDDK1348 KFVSNITRLS1358 SGPFRTITVR 1368 DTMSDLPEVR1378 NGASALEISY1388 NGEPQSWFQR1398 QLRGAQYQPI1408 LRDHICKDMS 1418 ALVAARMRHI1428 PLAPGSDWRD1438 LPNIEVRLSD1448 GTMARKLRYT1458 HHDRKNGRSS 1468 SGALRGVCSC1478 VEAGKACDPA1488 ARQFNTLIPW1498 CLPHTGNRHN1508 HWAGLYGRLE 1518 WDGFFSTTVT1528 NPEPMGKQGR1538 VLHPEQHRVV1548 SVRECARSQG1558 FPDTYRLFGN 1568 ILDKHRQVGN1578 AVPPPLAKAI1588 GLEIKLCMLA1598 KA
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| PDB ID: 7SFG Human DNMT1(729-1600) Bound to Zebularine-Containing 12mer dsDNA and Cofactor SAM | ||||||
| Method | X-ray diffraction | Resolution | 2.43 Å | Mutation | No | [2] |
| PDB Sequence |
RISWVGEAVK
739 TDGKKSYYKK749 VCIDAETLEV759 GDCVSVIPDD769 SSKPLYLARV779 TALWEDSSNG 789 QMFHAHWFCA799 GTDTVLGATS809 DPLELFLVDE819 CEDMQLSYIH829 SKVKVIYKAP 839 SENWAMEGGM849 DKTYFYQLWY869 DQDYARFESP879 PKTQPNKFKF892 CVSCARLAEM 902 RQKEIPRVLE912 QLEDLDSRVL922 YYSATKNGIL932 YRVGDGVYLP942 PEAFTFNIKP 963 VDEDLYPEHY973 RKYSDYIKGS983 NLDAPEPYRI993 GRIKEIFCPK1003 KSNGRPNETD 1013 IKIRVNKFYR1023 PENTHKSTPA1033 SYHADINLLY1043 WSDEEAVVDF1053 KAVQGRCTVE 1063 YGEDLPECVQ1073 VYSMGGPNRF1083 YFLEAYNAKS1093 KSFEDPPNHA1103 RKLPKLRTLD 1143 VFSGCGGLSE1153 GFHQAGISDT1163 LWAIEMWDPA1173 AQAFRLNNPG1183 STVFTEDCNI 1193 LLKLVMAGET1203 TNSRGQRLPQ1213 KGDVEMLCGG1223 PPCQGFSGMN1233 RFNSRTYSKF 1243 KNSLVVSFLS1253 YCDYYRPRFF1263 LLENVRNFVS1273 FKRSMVLKLT1283 LRCLVRMGYQ 1293 CTFGVLQAGQ1303 YGVAQTRRRA1313 IILAAAPGEK1323 LPLFPEPLHV1333 FAPRACQLSV 1343 VVDDKKFVSN1353 ITRLSSGPFR1363 TITVRDTMSD1373 LPEVRNGASA1383 LEISYNGEPQ 1393 SWFQRQLRGA1403 QYQPILRDHI1413 CKDMSALVAA1423 RMRHIPLAPG1433 SDWRDLPNIE 1443 VRLSDGTMAR1453 KLRYTHHDRK1463 NGRSSSGALR1473 GVCSCVEAGK1483 ACDPAARQFN 1493 TLIPWCLPHT1503 GNRHNHWAGL1513 YGRLEWDGFF1523 STTVTNPEPM1533 GKQGRVLHPE 1543 QHRVVSVREC1553 ARSQGFPDTY1563 RLFGNILDKH1573 RQVGNAVPPP1583 LAKAIGLEIK 1593 LCMLAKA
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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 .5CM or .5CM2 or .5CM3 or :35CM;style chemicals stick;color identity;select .A:1234 or .A:1498 or .A:1499 or .A:1500 or .A:1502 or .A:1503 or .A:1506 or .A:1507 or .A:1510 or .A:1513 or .A:1533 or .A:1534 or .A:1535; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7SFE Human DNMT1(729-1600) Bound to Zebularine-Containing 12mer dsDNA and Inhibitor GSK3830334A | ||||||
| Method | X-ray diffraction | Resolution | 2.55 Å | Mutation | No | [2] |
| PDB Sequence |
RISWVGEAVK
739 TDGKKSYYKK749 VCIDAETLEV759 GDCVSVIPDD769 SSKPLYLARV779 TALWEDSSNG 789 QMFHAHWFCA799 GTDTVLGATS809 DPLELFLVDE819 CEDMQLSYIH829 SKVKVIYKAP 839 SENWAMEGGM849 DPESLLEGDD859 GKTYFYQLWY869 DQDYARFESP879 PKTQPTEDNK 889 FKFCVSCARL899 AEMRQKEIPR909 VLEQLEDLDS919 RVLYYSATKN929 GILYRVGDGV 939 YLPPEAFTFN949 IKLSSPVKRP959 RKEPVDEDLY969 PEHYRKYSDY979 IKGSNLDAPE 989 PYRIGRIKEI999 FCPKKSNGRP1009 NETDIKIRVN1019 KFYRPENTHK1029 STPASYHADI 1039 NLLYWSDEEA1049 VVDFKAVQGR1059 CTVEYGEDLP1069 ECVQVYSMGG1079 PNRFYFLEAY 1089 NAKSKSFEDP1099 PNHARSKLPK1138 LRTLDVFSGC1148 GGLSEGFHQA1158 GISDTLWAIE 1168 MWDPAAQAFR1178 LNNPGSTVFT1188 EDCNILLKLV1198 MAGETTNSRG1208 QRLPQKGDVE 1218 MLCGGPPCQG1228 FSGMNRFNSR1238 TYSKFKNSLV1248 VSFLSYCDYY1258 RPRFFLLENV 1268 RNFVSFKRSM1278 VLKLTLRCLV1288 RMGYQCTFGV1298 LQAGQYGVAQ1308 TRRRAIILAA 1318 APGEKLPLFP1328 EPLHVFAPRA1338 CQLSVVVDDK1348 KFVSNITRLS1358 SGPFRTITVR 1368 DTMSDLPEVR1378 NGASALEISY1388 NGEPQSWFQR1398 QLRGAQYQPI1408 LRDHICKDMS 1418 ALVAARMRHI1428 PLAPGSDWRD1438 LPNIEVRLSD1448 GTMARKLRYT1458 HHDRKNGRSS 1468 SGALRGVCSC1478 VEAGKACDPA1488 ARQFNTLIPW1498 CLPHTGNRHN1508 HWAGLYGRLE 1518 WDGFFSTTVT1528 NPEPMGKQGR1538 VLHPEQHRVV1548 SVRECARSQG1558 FPDTYRLFGN 1568 ILDKHRQVGN1578 AVPPPLAKAI1588 GLEIKLCMLA1598 KA
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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 .5CM or .5CM2 or .5CM3 or :35CM;style chemicals stick;color identity;select .A:1498 or .A:1499 or .A:1500 or .A:1502 or .A:1503 or .A:1506 or .A:1507 or .A:1510 or .A:1513 or .A:1533 or .A:1534 or .A:1535; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6X9K Human DNMT1(729-1600) Bound to Zebularine-Containing 12mer dsDNA and Inhibitor GSK3685032A | ||||||
| Method | X-ray diffraction | Resolution | 2.65 Å | Mutation | No | [1] |
| PDB Sequence |
RISWVGEAVK
739 TDGKKSYYKK749 VCIDAETLEV759 GDCVSVIPDD769 SSKPLYLARV779 TALWEDSSNG 789 QMFHAHWFCA799 GTDTVLGATS809 DPLELFLVDE819 CEDMQLSYIH829 SKVKVIYKAP 839 SENWAMEGGM849 DPESLLEGDD859 GKTYFYQLWY869 DQDYARFESP879 PKTQPTEDNK 889 FKFCVSCARL899 AEMRQKEIPR909 VLEQLEDLDS919 RVLYYSATKN929 GILYRVGDGV 939 YLPPEAFTFN949 IKLSSPVKRP959 RKEPVDEDLY969 PEHYRKYSDY979 IKGSNLDAPE 989 PYRIGRIKEI999 FCPKKSNGRP1009 NETDIKIRVN1019 KFYRPENTHK1029 STPASYHADI 1039 NLLYWSDEEA1049 VVDFKAVQGR1059 CTVEYGEDLP1069 ECVQVYSMGG1079 PNRFYFLEAY 1089 NAKSKSFEDP1099 PNHARSKLPK1138 LRTLDVFSGC1148 GGLSEGFHQA1158 GISDTLWAIE 1168 MWDPAAQAFR1178 LNNPGSTVFT1188 EDCNILLKLV1198 MAGETTNSRG1208 QRLPQKGDVE 1218 MLCGGPPCQG1228 FSGMNRFNSR1238 TYSKFKNSLV1248 VSFLSYCDYY1258 RPRFFLLENV 1268 RNFVSFKRSM1278 VLKLTLRCLV1288 RMGYQCTFGV1298 LQAGQYGVAQ1308 TRRRAIILAA 1318 APGEKLPLFP1328 EPLHVFAPRA1338 CQLSVVVDDK1348 KFVSNITRLS1358 SGPFRTITVR 1368 DTMSDLPEVR1378 NGASALEISY1388 NGEPQSWFQR1398 QLRGAQYQPI1408 LRDHICKDMS 1418 ALVAARMRHI1428 PLAPGSDWRD1438 LPNIEVRLSD1448 GTMARKLRYT1458 HHDRKNGRSS 1468 SGALRGVCSC1478 VEAGKACDPA1488 ARQFNTLIPW1498 CLPHTGNRHN1508 HWAGLYGRLE 1518 WDGFFSTTVT1528 NPEPMGKQGR1538 VLHPEQHRVV1548 SVRECARSQG1558 FPDTYRLFGN 1568 ILDKHRQVGN1578 AVPPPLAKAI1588 GLEIKLCMLA1598 KA
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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 .5CM or .5CM2 or .5CM3 or :35CM;style chemicals stick;color identity;select .A:1498 or .A:1499 or .A:1500 or .A:1502 or .A:1503 or .A:1506 or .A:1507 or .A:1510 or .A:1513 or .A:1533 or .A:1534; 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 | Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia. Nat Cancer. 2021 Oct;2(10):1002-1017. Epub 2021 Sep 27. | ||||
| REF 2 | Structural characterization of dicyanopyridine containing DNMT1-selective, non-nucleoside inhibitors. Structure. 2022 Jun 2;30(6):793-802.e5. | ||||
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