Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T09826 | Target Info | |||
| Target Name | DNA topoisomerase I (TOP1) | ||||
| Synonyms | DNA topoisomerase I | ||||
| Target Type | Successful Target | ||||
| Gene Name | TOP1 | ||||
| Biochemical Class | Topoisomerase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Topotecan | Ligand Info | |||||
| Structure Description | HUMAN DNA TOPOISOMERASE I (70 KDA) IN COMPLEX WITH THE POISON TOPOTECAN AND COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX | PDB:1K4T | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [1] |
| PDB Sequence |
QKWKWWEEER
210 YPEGIKWKFL220 EHKGPVFAPP230 YEPLPENVKF240 YYDGKVMKLS250 PKAEEVATFF 260 AKMLDHEYTT270 KEIFRKNFFK280 DWRKEMTNEE290 KNIITNLSKC300 DFTQMSQYFK 310 AQTEARKQMS320 KEEKLKIKEE330 NEKLLKEYGF340 CIMDNHKERI350 ANFKIEPPGL 360 FRGRGNHPKM370 GMLKRRIMPE380 DIIINCSKDA390 KVPSPPPGHK400 WKEVRHDNKV 410 TWLVSWTENI420 QGSIKYIMLN430 PSSRIKGEKD440 WQKYETARRL450 KKCVDKIRNQ 460 YREDWKSKEM470 KVRQRAVALY480 FIDKLALRAG490 NEKEEGETAD500 TVGCCSLRVE 510 HINLHPELDG520 QEYVVEFDFL530 GKDSIRYYNK540 VPVEKRVFKN550 LQLFMENKQP 560 EDDLFDRLNT570 GILNKHLQDL580 MEGLTAKVFR590 TYNASITLQQ600 QLKELTAPDE 610 NIPAKILSYN620 RANRAVAILC630 NHQRAPPKTF640 EKSMMNLQTK650 IDAKKEQLAD 660 ARRDLKSAKA670 DAKVMKDAKT680 KKVVESKKKA690 VQRLEEQLMK700 LEVQATDREE 710 NKQIALGTSK720 LNLDPRITVA731 WCKKWGVPIE741 KIYNKTQREK751 FAWAIDMADE 761 DYEF
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Camptothecin | Ligand Info | |||||
| Structure Description | Human DNA Topoisomerase I (70 Kda) In Complex With The Poison Camptothecin and Covalent Complex With A 22 Base Pair DNA Duplex | PDB:1T8I | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | Yes | [2] |
| PDB Sequence |
QKWKWWEEER
210 YPEGIKWKFL220 EHKGPVFAPP230 YEPLPENVKF240 YYDGKVMKLS250 PKAEEVATFF 260 AKMLDHEYTT270 KEIFRKNFFK280 DWRKEMTNEE290 KNIITNLSKC300 DFTQMSQYFK 310 AQTEARKQMS320 KEEKLKIKEE330 NEKLLKEYGF340 CIMDNHKERI350 ANFKIEPPGL 360 FRGRGNHPKM370 GMLKRRIMPE380 DIIINCSKDA390 KVPSPPPGHK400 WKEVRHDNKV 410 TWLVSWTENI420 QGSIKYIMLN430 PSSRIKGEKD440 WQKYETARRL450 KKCVDKIRNQ 460 YREDWKSKEM470 KVRQRAVALY480 FIDKLALRAG490 NEKEEGETAD500 TVGCCSLRVE 510 HINLHPELDG520 QEYVVEFDFL530 GKDSIRYYNK540 VPVEKRVFKN550 LQLFMENKQP 560 EDDLFDRLNT570 GILNKHLQDL580 MEGLTAKVFR590 TYNASITLQQ600 QLKELTAPDE 610 NIPAKILSYN620 RANRAVAILC630 NHQRAPPKTF640 EKSMMNLQTK650 IDAKKEQLAD 660 ARRDLKSAKA670 DAKVMKDAKT680 KKVVESKKKA690 VQRLEEQLMK700 LEVQATDREE 710 NKQIALGTSK720 LNLDPRITVA731 WCKKWGVPIE741 KIYNKTQREK751 FAWAIDMADE 761 DYEF
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| Ligand Name: Phosphonotyrosine | Ligand Info | |||||
| Structure Description | HUMAN DNA TOPOISOMERASE I (70 KDA) IN COMPLEX WITH THE POISON TOPOTECAN AND COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX | PDB:1K4T | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [1] |
| PDB Sequence |
QKWKWWEEER
210 YPEGIKWKFL220 EHKGPVFAPP230 YEPLPENVKF240 YYDGKVMKLS250 PKAEEVATFF 260 AKMLDHEYTT270 KEIFRKNFFK280 DWRKEMTNEE290 KNIITNLSKC300 DFTQMSQYFK 310 AQTEARKQMS320 KEEKLKIKEE330 NEKLLKEYGF340 CIMDNHKERI350 ANFKIEPPGL 360 FRGRGNHPKM370 GMLKRRIMPE380 DIIINCSKDA390 KVPSPPPGHK400 WKEVRHDNKV 410 TWLVSWTENI420 QGSIKYIMLN430 PSSRIKGEKD440 WQKYETARRL450 KKCVDKIRNQ 460 YREDWKSKEM470 KVRQRAVALY480 FIDKLALRAG490 NEKEEGETAD500 TVGCCSLRVE 510 HINLHPELDG520 QEYVVEFDFL530 GKDSIRYYNK540 VPVEKRVFKN550 LQLFMENKQP 560 EDDLFDRLNT570 GILNKHLQDL580 MEGLTAKVFR590 TYNASITLQQ600 QLKELTAPDE 610 NIPAKILSYN620 RANRAVAILC630 NHQRAPPKTF640 EKSMMNLQTK650 IDAKKEQLAD 660 ARRDLKSAKA670 DAKVMKDAKT680 KKVVESKKKA690 VQRLEEQLMK700 LEVQATDREE 710 NKQIALGTSK720 LNLDPRITVA731 WCKKWGVPIE741 KIYNKTQREK751 FAWAIDMADE 761 DYEF
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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 .PTR or .PTR2 or .PTR3 or :3PTR;style chemicals stick;color identity;select .A:443 or .A:444 or .A:488 or .A:532 or .A:590 or .A:591 or .A:594 or .A:595 or .A:630 or .A:632 or .A:718 or .A:719 or .A:720 or .A:721 or .A:722 or .A:724 or .A:725; 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: 2-(1-Dimethylaminomethyl-2-hydroxy-8-hydroxymethyl-9-oxo-9,11-dihydro-indolizino[1,2-B]quinolin-7-YL)-2-hydroxy-butyric acid | Ligand Info | |||||
| Structure Description | HUMAN DNA TOPOISOMERASE I (70 KDA) IN COMPLEX WITH THE POISON TOPOTECAN AND COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX | PDB:1K4T | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [1] |
| PDB Sequence |
QKWKWWEEER
210 YPEGIKWKFL220 EHKGPVFAPP230 YEPLPENVKF240 YYDGKVMKLS250 PKAEEVATFF 260 AKMLDHEYTT270 KEIFRKNFFK280 DWRKEMTNEE290 KNIITNLSKC300 DFTQMSQYFK 310 AQTEARKQMS320 KEEKLKIKEE330 NEKLLKEYGF340 CIMDNHKERI350 ANFKIEPPGL 360 FRGRGNHPKM370 GMLKRRIMPE380 DIIINCSKDA390 KVPSPPPGHK400 WKEVRHDNKV 410 TWLVSWTENI420 QGSIKYIMLN430 PSSRIKGEKD440 WQKYETARRL450 KKCVDKIRNQ 460 YREDWKSKEM470 KVRQRAVALY480 FIDKLALRAG490 NEKEEGETAD500 TVGCCSLRVE 510 HINLHPELDG520 QEYVVEFDFL530 GKDSIRYYNK540 VPVEKRVFKN550 LQLFMENKQP 560 EDDLFDRLNT570 GILNKHLQDL580 MEGLTAKVFR590 TYNASITLQQ600 QLKELTAPDE 610 NIPAKILSYN620 RANRAVAILC630 NHQRAPPKTF640 EKSMMNLQTK650 IDAKKEQLAD 660 ARRDLKSAKA670 DAKVMKDAKT680 KKVVESKKKA690 VQRLEEQLMK700 LEVQATDREE 710 NKQIALGTSK720 LNLDPRITVA731 WCKKWGVPIE741 KIYNKTQREK751 FAWAIDMADE 761 DYEF
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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 .TTG or .TTG2 or .TTG3 or :3TTG;style chemicals stick;color identity;select .A:352 or .A:356 or .A:364 or .A:532 or .A:533 or .A:632 or .A:718 or .A:722; 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: [(2S,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methylsulfanylphosphonic acid | Ligand Info | |||||
| Structure Description | HUMAN DNA TOPOISOMERASE I (70 KDA) IN COMPLEX WITH THE POISON TOPOTECAN AND COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX | PDB:1K4T | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [1] |
| PDB Sequence |
QKWKWWEEER
210 YPEGIKWKFL220 EHKGPVFAPP230 YEPLPENVKF240 YYDGKVMKLS250 PKAEEVATFF 260 AKMLDHEYTT270 KEIFRKNFFK280 DWRKEMTNEE290 KNIITNLSKC300 DFTQMSQYFK 310 AQTEARKQMS320 KEEKLKIKEE330 NEKLLKEYGF340 CIMDNHKERI350 ANFKIEPPGL 360 FRGRGNHPKM370 GMLKRRIMPE380 DIIINCSKDA390 KVPSPPPGHK400 WKEVRHDNKV 410 TWLVSWTENI420 QGSIKYIMLN430 PSSRIKGEKD440 WQKYETARRL450 KKCVDKIRNQ 460 YREDWKSKEM470 KVRQRAVALY480 FIDKLALRAG490 NEKEEGETAD500 TVGCCSLRVE 510 HINLHPELDG520 QEYVVEFDFL530 GKDSIRYYNK540 VPVEKRVFKN550 LQLFMENKQP 560 EDDLFDRLNT570 GILNKHLQDL580 MEGLTAKVFR590 TYNASITLQQ600 QLKELTAPDE 610 NIPAKILSYN620 RANRAVAILC630 NHQRAPPKTF640 EKSMMNLQTK650 IDAKKEQLAD 660 ARRDLKSAKA670 DAKVMKDAKT680 KKVVESKKKA690 VQRLEEQLMK700 LEVQATDREE 710 NKQIALGTSK720 LNLDPRITVA731 WCKKWGVPIE741 KIYNKTQREK751 FAWAIDMADE 761 DYEF
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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 .TGP or .TGP2 or .TGP3 or :3TGP;style chemicals stick;color identity;select .A:364 or .A:717 or .A:718 or .A:721 or .A:722; 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: 2,10-Dihydroxy-12-(beta-D-glucopyranosyl)-6,7,12,13-tetrahydroindolo[2,3-A]pyrrolo[3,4-C]carbazole-5,7-dione | Ligand Info | |||||
| Structure Description | Human DNA Topoisomerase I (70 Kda) In Complex With The Indolocarbazole SA315F and Covalent Complex With A 22 Base Pair DNA Duplex | PDB:1SEU | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | Yes | [2] |
| PDB Sequence |
QKWKWWEEER
210 YPEGIKWKFL220 EHKGPVFAPP230 YEPLPENVKF240 YYDGKVMKLS250 PKAEEVATFF 260 AKMLDHEYTT270 KEIFRKNFFK280 DWRKEMTNEE290 KNIITNLSKC300 DFTQMSQYFK 310 AQTEARKQMS320 KEEKLKIKEE330 NEKLLKEYGF340 CIMDNHKERI350 ANFKIEPPGL 360 FRGRGNHPKM370 GMLKRRIMPE380 DIIINCSKDA390 KVPSPPPGHK400 WKEVRHDNKV 410 TWLVSWTENI420 QGSIKYIMLN430 PSSRIKGEKD440 WQKYETARRL450 KKCVDKIRNQ 460 YREDWKSKEM470 KVRQRAVALY480 FIDKLALRAG490 NEKEEGETAD500 TVGCCSLRVE 510 HINLHPELDG520 QEYVVEFDFL530 GKDSIRYYNK540 VPVEKRVFKN550 LQLFMENKQP 560 EDDLFDRLNT570 GILNKHLQDL580 MEGLTAKVFR590 TYNASITLQQ600 QLKELTAPDE 610 NIPAKILSYN620 RANRAVAILC630 NHQRAPPKTF640 EKSMMNLQTK650 IDAKKEQLAD 660 ARRDLKSAKA670 DAKVMKDAKT680 KKVVESKKKA690 VQRLEEQLMK700 LEVQATDREE 710 NKQIALGTSK720 LSLDPRITVA731 WCKKWGVPIE741 KIYNKTQREK751 FAWAIDMADE 761 DYEF
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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 .SA3 or .SA32 or .SA33 or :3SA3;style chemicals stick;color identity;select .A:351 or .A:352 or .A:356 or .A:364 or .A:425 or .A:426 or .A:428 or .A:721 or .A:722 or .A:751; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 4-(5,11-Dioxo-5H-indeno[1,2-C]isoquinolin-6(11H)-YL)butanoate | Ligand Info | |||||
| Structure Description | Human DNA Topoisomerase I (70 Kda) In Complex With The Indenoisoquinoline MJ-II-38 and Covalent Complex With A 22 Base Pair DNA Duplex | PDB:1SC7 | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | Yes | [2] |
| PDB Sequence |
EEQKWKWWEE
208 ERYPEGIKWK218 FLEHKGPVFA228 PPYEPLPENV238 KFYYDGKVMK248 LSPKAEEVAT 258 FFAKMLDHEY268 TTKEIFRKNF278 FKDWRKEMTN288 EEKNIITNLS298 KCDFTQMSQY 308 FKAQTEARKQ318 MSKEEKLKIK328 EENEKLLKEY338 GFCIMDNHKE348 RIANFKIEPP 358 GLFRGRGNHP368 KMGMLKRRIM378 PEDIIINCSK388 DAKVPSPPPG398 HKWKEVRHDN 408 KVTWLVSWTE418 NIQGSIKYIM428 LNPSSRIKGE438 KDWQKYETAR448 RLKKCVDKIR 458 NQYREDWKSK468 EMKVRQRAVA478 LYFIDKLALR488 AGNEKEEGET498 ADTVGCCSLR 508 VEHINLHPEL518 DGQEYVVEFD528 FLGKDSIRYY538 NKVPVEKRVF548 KNLQLFMENK 558 QPEDDLFDRL568 NTGILNKHLQ578 DLMEGLTAKV588 FRTYNASITL598 QQQLKELTAP 608 DENIPAKILS618 YNRANRAVAI628 LCNHQRAPPK638 TFEKSMMNLQ648 TKIDAKKEQL 658 ADARRDLKSA668 KADAKVMKDA678 KTKKVVESKK688 KAVQRLEEQL698 MKLEVQATDR 708 EENKQIALGT718 SKLNLDPRIT729 VAWCKKWGVP739 IEKIYNKTQR749 EKFAWAIDMA 759 DEDYEF
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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 .M38 or .M382 or .M383 or :3M38;style chemicals stick;color identity;select .A:351 or .A:352 or .A:364 or .A:425 or .A:718 or .A:722; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 2,3-Dimethoxy-12H-[1,3]dioxolo[5,6]indeno[1,2-C]isoquinolin-6-ium | Ligand Info | |||||
| Structure Description | Human DNA topoisomerase I (70 kDa) in complex with the indenoisoquinoline AI-III-52 and covalent complex with a 22 base pair DNA duplex | PDB:1TL8 | ||||
| Method | X-ray diffraction | Resolution | 3.10 Å | Mutation | Yes | [3] |
| PDB Sequence |
QKWKWWEEER
210 YPEGIKWKFL220 EHKGPVFAPP230 YEPLPENVKF240 YYDGKVMKLS250 PKAEEVATFF 260 AKMLDHEYTT270 KEIFRKNFFK280 DWRKEMTNEE290 KNIITNLSKC300 DFTQMSQYFK 310 AQTEARKQMS320 KEEKLKIKEE330 NEKLLKEYGF340 CIMDNHKERI350 ANFKIEPPGL 360 FRGRGNHPKM370 GMLKRRIMPE380 DIIINCSKDA390 KVPSPPPGHK400 WKEVRHDNKV 410 TWLVSWTENI420 QGSIKYIMLN430 PSSRIKGEKD440 WQKYETARRL450 KKCVDKIRNQ 460 YREDWKSKEM470 KVRQRAVALY480 FIDKLALRAG490 NEKEEGETAD500 TVGCCSLRVE 510 HINLHPELDG520 QEYVVEFDFL530 GKDSIRYYNK540 VPVEKRVFKN550 LQLFMENKQP 560 EDDLFDRLNT570 GILNKHLQDL580 MEGLTAKVFR590 TYNASITLQQ600 QLKELTAPDE 610 NIPAKILSYN620 RANRAVAILC630 NHQRAPPKTF640 EKSMMNLQTK650 IDAKKEQLAD 660 ARRDLKSAKA670 DAKVMKDAKT680 KKVVESKKKA690 VQRLEEQLMK700 LEVQATDREE 710 NKQIALGTSK720 LNLDPRITVA731 WCKKWGVPIE741 KIYNKTQREK751 FAWAIDMADE 761 DYEF
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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 .AI3 or .AI32 or .AI33 or :3AI3;style chemicals stick;color identity;select .A:352 or .A:356 or .A:364 or .A:425 or .A:718 or .A:722; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: [(2S,3S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methylsulfanylphosphonic acid | Ligand Info | |||||
| Structure Description | Human DNA topoisomerase I (70 kDa) in complex with the indenoisoquinoline AI-III-52 and covalent complex with a 22 base pair DNA duplex | PDB:1TL8 | ||||
| Method | X-ray diffraction | Resolution | 3.10 Å | Mutation | Yes | [3] |
| PDB Sequence |
QKWKWWEEER
210 YPEGIKWKFL220 EHKGPVFAPP230 YEPLPENVKF240 YYDGKVMKLS250 PKAEEVATFF 260 AKMLDHEYTT270 KEIFRKNFFK280 DWRKEMTNEE290 KNIITNLSKC300 DFTQMSQYFK 310 AQTEARKQMS320 KEEKLKIKEE330 NEKLLKEYGF340 CIMDNHKERI350 ANFKIEPPGL 360 FRGRGNHPKM370 GMLKRRIMPE380 DIIINCSKDA390 KVPSPPPGHK400 WKEVRHDNKV 410 TWLVSWTENI420 QGSIKYIMLN430 PSSRIKGEKD440 WQKYETARRL450 KKCVDKIRNQ 460 YREDWKSKEM470 KVRQRAVALY480 FIDKLALRAG490 NEKEEGETAD500 TVGCCSLRVE 510 HINLHPELDG520 QEYVVEFDFL530 GKDSIRYYNK540 VPVEKRVFKN550 LQLFMENKQP 560 EDDLFDRLNT570 GILNKHLQDL580 MEGLTAKVFR590 TYNASITLQQ600 QLKELTAPDE 610 NIPAKILSYN620 RANRAVAILC630 NHQRAPPKTF640 EKSMMNLQTK650 IDAKKEQLAD 660 ARRDLKSAKA670 DAKVMKDAKT680 KKVVESKKKA690 VQRLEEQLMK700 LEVQATDREE 710 NKQIALGTSK720 LNLDPRITVA731 WCKKWGVPIE741 KIYNKTQREK751 FAWAIDMADE 761 DYEF
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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 .TPC or .TPC2 or .TPC3 or :3TPC;style chemicals stick;color identity;select .A:717 or .A:718 or .A:721 or .A:722; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | The mechanism of topoisomerase I poisoning by a camptothecin analog. Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15387-92. | ||||
| REF 2 | Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex. J Med Chem. 2005 Apr 7;48(7):2336-45. | ||||
| REF 3 | Synthesis and mechanism of action studies of a series of norindenoisoquinoline topoisomerase I poisons reveal an inhibitor with a flipped orientation in the ternary DNA-enzyme-inhibitor complex as determined by X-ray crystallographic analysis. J Med Chem. 2005 Jul 28;48(15):4803-14. | ||||
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