Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T40812 | Target Info | |||
| Target Name | Poly [ADP-ribose] polymerase 2 (PARP2) | ||||
| Synonyms | pADPRT-2; hPARP-2; Protein poly-ADP-ribosyltransferase PARP2; Poly[ADP-ribose] synthase 2; PARP-2; NAD(+) ADP-ribosyltransferase 2; DNA ADP-ribosyltransferase PARP2; ARTD2; ADPRTL2; ADPRT2; ADPRT-2; ADP-ribosyltransferase diphtheria toxin-like 2 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | PARP2 | ||||
| Biochemical Class | Glycosyltransferases | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Olaparib | Ligand Info | |||||
| Structure Description | HUMAN ARTD2 (PARP2) - CATALYTIC DOMAIN IN COMPLEX WITH OLAPARIB | PDB:4TVJ | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [1] |
| PDB Sequence |
DLGTENLYFQ
232 SMDLRVQELI242 KLICNVQAME252 EMMMEMKYNT262 KKAPLGKLTV272 AQIKAGYQSL 282 KKIEDCIRAG292 QHGRALMEAC302 NEFYTRIPHD312 FGLRTPPLIR322 TQKELSEKIQ 332 LLEALGDIEI342 AIKLVKTELQ352 SPEHPLDQHY362 RNLHCALRPL372 DHESYEFKVI 382 SQYLQSTHAP392 THSDYTMTLL402 DLFEVEKDGE412 KEAFREDLHN422 RMLLWHGSRM 432 SNWVGILSHG442 LRIAHPEAPI452 TGYMFGKGIY462 FADMSSKSAN472 YCFASRLKNT 482 GLLLLSEVAL492 GQCNELLEAN502 PKAEGLLQGK512 HSTKGLGKMA522 PSSAHFVTLN 532 GSTVPLGPAS542 DTGILNPDGY552 TLNYNEYIVY562 NPNQVRMRYL572 LKVQFNF |
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GLU335
3.338
TRP427
3.958
HIS428
3.306
GLY429
2.798
SER430
4.997
GLY442
4.358
LEU443
3.847
ARG444
3.017
ILE445
4.108
ALA446
3.800
HIS447
4.702
GLY454
5.000
|
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| Ligand Name: Talazoparib | Ligand Info | |||||
| Structure Description | Structure of PARP2 catalytic domain bound to inhibitor BMN 673 | PDB:4PJV | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [2] |
| PDB Sequence |
MDLRVQELIK
243 LICNVQAMEE253 MMMEMKYNTK263 KAPLGKLTVA273 QIKAGYQSLK283 KIEDCIRAGR 296 ALMEACNEFY306 TRIPHDFGLR316 TPPLIRTQKE326 LSEKIQLLEA336 LGDIEIAIKL 346 VKTEEHPLDQ360 HYRNLHCALR370 PLDHESYEFK380 VISQYLQSTH390 APTHSDYTMT 400 LLDLFEVEKD410 GEKEAFREDL420 HNRMLLWHGS430 RMSNWVGILS440 HGLRIAHPEA 450 PITGYMFGKG460 IYFADMSSKS470 ANYCFASRLK480 NTGLLLLSEV490 ALGQCNELLE 500 ANPKAEGLLQ510 GKHSTKGLGK520 MAPSSAHFVT530 LNGSTVPLGP540 ASDTGILNPD 550 GYTLNYNEYI560 VYNPNQVRMR570 YLLKVQFNF
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| Ligand Name: ABT-888 | Ligand Info | |||||
| Structure Description | Human poly(ADP-ribose) polymerase 2, catalytic fragment in complex with an inhibitor ABT-888 | PDB:3KJD | ||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [3] |
| PDB Sequence |
TENLYFQSMD
235 LRVQELIKLI245 CNVQAMEEMM255 MEMKYNTKKA265 PLGKLTVAQI275 KAGYQSLKKI 285 EDCIRAGQHG295 RALMEACNEF305 YTRIPHDFGL315 RTPPLIRTQK325 ELSEKIQLLE 335 ALGDIEIAIK345 LVKSPEHPLD359 QHYRNLHCAL369 RPLDHESYEF379 KVISQYLQST 389 HAPTHSDYTM399 TLLDLFEVEK409 DGEKEAFRED419 LHNRMLLWHG429 SRMSNWVGIL 439 SHGLRIAHPE449 APITGYMFGK459 GIYFADMSSK469 SANYCFASRL479 KNTGLLLLSE 489 VALGQCNELL499 EANPKAEGLL509 QGKHSTKGLG519 KMAPSSAHFV529 TLNGSTVPLG 539 PASDTGILNP549 DGYTLNYNEY559 IVYNPNQVRM569 RYLLKVQFNF579 |
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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 .78P or .78P2 or .78P3 or :378P;style chemicals stick;color identity;select .A:328 or .A:332 or .A:335 or .A:427 or .A:428 or .A:429 or .A:455 or .A:462 or .A:463 or .A:464 or .A:469 or .A:470 or .A:473 or .A:558; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 3-aminobenzamide | Ligand Info | |||||
| Structure Description | Human poly(ADP-ribose) polymerase 2, catalytic fragment in complex with an inhibitor 3-aminobenzamide | PDB:3KCZ | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [3] |
| PDB Sequence |
LGTENLYFQS
233 MDLRVQELIK243 LICNVQAMEE253 MMMEMKYNTK263 KAPLGKLTVA273 QIKAGYQSLK 283 KIEDCIRAGQ293 HGRALMEACN303 EFYTRIPHDF313 GLRTPPLIRT323 QKELSEKIQL 333 LEALGDIEIA343 IKLVKTELQS353 PEHPLDQHYR363 NLHCALRPLD373 HESYEFKVIS 383 QYLQSTHAPT393 HSDYTMTLLD403 LFEVEKDGEK413 EAFREDLHNR423 MLLWHGSRMS 433 NWVGILSHGL443 RIAHPEAPIT453 GYMFGKGIYF463 ADMSSKSANY473 CFASRLKNTG 483 LLLLSEVALG493 QCNELLEANP503 KAEGLLQGKH513 STKGLGKMAP523 SSAHFVTLNG 533 STVPLGPASD543 TGILGYTLNY556 NEYIVYNPNQ566 VRMRYLLKVQ576 FNF |
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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 .3AB or .3AB2 or .3AB3 or :33AB;style chemicals stick;color identity;select .A:427 or .A:428 or .A:429 or .A:462 or .A:463 or .A:464 or .A:469 or .A:470 or .A:473 or .A:558; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: EB-47 | Ligand Info | |||||
| Structure Description | Crystal structure of constitutively active PARP-2 | PDB:5DSY | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [4] |
| PDB Sequence |
PESQLDLRVQ
226 ELIKLICNQS340 PEHPLDQHYR350 NLHCALRPLD360 HESYEFKVIS370 QYLQSTHAPT 380 HSDYTMTLLD390 LFEVEKDGEK400 EAFREDLHNR410 MLLWHGSRMS420 NWVGILSHGL 430 RIAPPEAPIT440 GYMFGKGIYF450 ADMSSKSANY460 CFASRLKNTG470 LLLLSEVALG 480 QCNELLEANP490 KAEGLLQGKH500 STKGLGKMAP510 SSAHFVTLNG520 STVPLGPASD 530 TGILNPDGYT540 LNYNEYIVYN550 PNQVRMRYLL560 KVQFNFLQ
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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 .UHB or .UHB2 or .UHB3 or :3UHB;style chemicals stick;color identity;select .A:414 or .A:415 or .A:416 or .A:417 or .A:421 or .A:424 or .A:425 or .A:428 or .A:429 or .A:430 or .A:431 or .A:432 or .A:433 or .A:434 or .A:442 or .A:449 or .A:450 or .A:451 or .A:456 or .A:457 or .A:460 or .A:545; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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TRP414
3.571
HIS415
2.875
GLY416
2.877
SER417
2.532
ASN421
3.531
GLY424
3.204
ILE425
3.521
HIS428
4.225
GLY429
2.950
LEU430
3.762
ARG431
3.050
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 2-(3-Methoxypropyl)-3-Oxo-2,3-Dihydro-1h-Isoindole-4-Carboxamide | Ligand Info | |||||
| Structure Description | Structure of PARP2 catalytic domain bound to an isoindolinone inhibitor | PDB:4ZZX | ||||
| Method | X-ray diffraction | Resolution | 1.65 Å | Mutation | No | [5] |
| PDB Sequence |
ESQLDLRVQE
240 LIKLICNVQA250 MEEMMMEMKY260 NTKKAPLGKL270 TVAQIKAGYQ280 SLKKIEDCIR 290 AGQHGRALME300 ACNEFYTRIP310 HDFGLRTPPL320 IRTQKELSEK330 IQLLEALGDI 340 EIAIKLVKTE350 LQSPEHPLDQ360 HYRNLHCALR370 PLDHESYEFK380 VISQYLQSTH 390 APTHSDYTMT400 LLDLFEVEKD410 GEKEAFREDL420 HNRMLLWHGS430 RMSNWVGILS 440 HGLRIAPPEA450 PITGYMFGKG460 IYFADMSSKS470 ANYCFASRLK480 NTGLLLLSEV 490 ALGQCNELLE500 ANPKAEGLLQ510 GKHSTKGLGK520 MAPSSAHFVT530 LNGSTVPLGP 540 ASDTGILNGY552 TLNYNEYIVY562 NPNQVRMRYL572 LKVQFNFLQL582 W |
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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 .FSU or .FSU2 or .FSU3 or :3FSU;style chemicals stick;color identity;select .A:328 or .A:331 or .A:332 or .A:335 or .A:427 or .A:428 or .A:429 or .A:454 or .A:455 or .A:462 or .A:463 or .A:464 or .A:469 or .A:470 or .A:473 or .A:558; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 2-[1-(4,4-Difluorocyclohexyl)-piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide | Ligand Info | |||||
| Structure Description | Structure of human PARP2 catalytic domain bound to an isoindolinone inhibitor | PDB:4ZZY | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [5] |
| PDB Sequence |
ESQLDLRVQE
240 LIKLICNVQA250 MEEMMMEMKY260 NTKKAPLGKL270 TVAQIKAGYQ280 SLKKIEDCIR 290 AGQHGRALME300 ACNEFYTRIP310 HDFGLRTPPL320 IRTQKELSEK330 IQLLEALGDI 340 EIAIKLVKTE350 LQSPEHPLDQ360 HYRNLHCALR370 PLDHESYEFK380 VISQYLQSTH 390 APTHSDYTMT400 LLDLFEVEKD410 GEKEAFREDL420 HNRMLLWHGS430 RMSNWVGILS 440 HGLRIAPPEA450 PITGYMFGKG460 IYFADMSSKS470 ANYCFASRLK480 NTGLLLLSEV 490 ALGQCNELLE500 ANPKAEGLLQ510 GKHSTKGLGK520 MAPSSAHFVT530 LNGSTVPLGP 540 ASDTGILNGY552 TLNYNEYIVY562 NPNQVRMRYL572 LKVQFNFLQL582 W |
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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 .D7N or .D7N2 or .D7N3 or :3D7N;style chemicals stick;color identity;select .A:328 or .A:331 or .A:332 or .A:427 or .A:428 or .A:429 or .A:451 or .A:454 or .A:455 or .A:462 or .A:463 or .A:464 or .A:469 or .A:470 or .A:473 or .A:557 or .A:558; 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 | Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors. J Med Chem. 2017 Feb 23;60(4):1262-1271. | ||||
| REF 2 | Structural basis for the inhibition of poly(ADP-ribose) polymerases 1 and 2 by BMN 673, a potent inhibitor derived from dihydropyridophthalazinone. Acta Crystallogr F Struct Biol Commun. 2014 Sep;70(Pt 9):1143-9. | ||||
| REF 3 | Crystal structure of the catalytic domain of human PARP2 in complex with PARP inhibitor ABT-888. Biochemistry. 2010 Feb 16;49(6):1056-8. | ||||
| REF 4 | PARP-1 Activation Requires Local Unfolding of an Autoinhibitory Domain. Mol Cell. 2015 Dec 3;60(5):755-768. | ||||
| REF 5 | Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy. J Med Chem. 2015 Sep 10;58(17):6875-98. | ||||
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