Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T06273 | Target Info | |||
| Target Name | Poly [ADP-ribose] polymerase 1 (PARP1) | ||||
| Synonyms | Protein poly-ADP-ribosyltransferase PARP1; Poly[ADP-ribose] synthetase-1; Poly[ADP-ribose] synthase 1; Poly(ADP-ribose)polymerase-1; PPOL; PARP-1; NAD(+)Poly [ADP-ribose] polymerase-1 ADP-ribosyltransferase-1; NAD(+) ADP-ribosyltransferase-1; NAD(+) ADP-ribosyltransferase 1; DNA ADP-ribosyltransferase PARP1; ARTD1; ADPRT 1; ADPRT; ADP-ribosyltransferase diphtheria toxin-like 1 | ||||
| Target Type | Successful Target | ||||
| Gene Name | PARP1 | ||||
| Biochemical Class | Glycosyltransferases | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Talazoparib | Ligand Info | |||
| Canonical SMILES | CN1C(=NC=N1)C2C(NC3=CC(=CC4=C3C2=NNC4=O)F)C5=CC=C(C=C5)F | ||||
| InChI | 1S/C19H14F2N6O/c1-27-18(22-8-23-27)15-16(9-2-4-10(20)5-3-9)24-13-7-11(21)6-12-14(13)17(15)25-26-19(12)28/h2-8,15-16,24H,1H3,(H,26,28)/t15-,16-/m1/s1 | ||||
| InChIKey | HWGQMRYQVZSGDQ-HZPDHXFCSA-N | ||||
| PubChem Compound ID | 135565082 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 4UND HUMAN ARTD1 (PARP1) - CATALYTIC DOMAIN IN COMPLEX WITH INHIBITOR TALAZOPARIB | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [1] |
| PDB Sequence |
NLYFQSMKSK
664 LPKPVQDLIK674 MIFDVESMKK684 AMVEYEIDLQ694 KMPLGKLSKR704 QIQAAYSILS 714 EVQQAVSQGS724 SDSQILDLSN734 RFYTLIPHDF744 GMKKPPLLNN754 ADSVQAKAEM 764 LDNLLDIEVA774 YSLLRGGSDD784 SSKDPIDVNY794 EKLKTDIKVV804 DRDSEEAEII 814 RKYVKNTHAT824 THNAYDLEVI834 DIFKIEREGE844 CQRYKPFKQL854 HNRRLLWHGS 864 RTTNFAGILS874 QGLRIAPPEA884 PVTGYMFGKG894 IYFADMVSKS904 ANYCHTSQGD 914 PIGLILLGEV924 ALGNMYELKH934 ASHISKLPKG944 KHSVKGLGKT954 TPDPSANISL 964 DGVDVPLGTG974 ISSGVNDTSL984 LYNEYIVYDI994 AQVNLKYLLK1004 LKFNFK |
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GLN759
4.071
GLU763
2.449
ASP766
4.963
TRP861
3.991
HIS862
3.107
GLY863
2.656
SER864
4.859
ARG878
4.796
THR887
4.685
GLY888
4.063
TYR889
3.710
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| PDB ID: 4PJT Structure of PARP1 catalytic domain bound to inhibitor BMN 673 | ||||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | No | [2] |
| PDB Sequence |
KSKLPKPVQD
671 LIKMIFDVES681 MKKAMVEYEI691 DLQKMPLGKL701 SKRQIQAAYS711 ILSEVQQAVS 721 QDSQILDLSN734 RFYTLIPHDF744 KPPLLNNADS757 VQAKVEMLDN767 LLDIEVAYSL 777 LRGSKDPIDV792 NYEKLKTDIK802 VVDRDSEEAE812 IIRKYVKNTH822 ATTHNAYDLE 832 VIDIFKIERE842 GECQRYKPFK852 QLHNRRLLWH862 GSRTTNFAGI872 LSQGLRIAPP 882 EAPVTGYMFG892 KGIYFADMVS902 KSANYCHTSQ912 GDPIGLILLG922 EVALGNMYEL 932 KHASHISKLP942 KGKHSVKGLG952 KTTPDPSANI962 SLDGVDVPLG972 TGISSGVNDT 982 SLLYNEYIVY992 DIAQVNLKYL1002 LKLKFNFK
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| PDB ID: 7KK3 Structure of the catalytic domain of PARP1 in complex with talazoparib | ||||||
| Method | X-ray diffraction | Resolution | 2.06 Å | Mutation | No | [3] |
| PDB Sequence |
KSKLPKPVQD
671 LIKMIFDVES681 MKKAMVEYEI691 DLQKMPLGKL701 SKRQIQAAYS711 ILSEVQQAVS 721 QDSQILDLSN734 RFYTLIPHDF744 KPPNNADSVQ759 AKVEMLDNLL769 DIEVAYSLLR 779 GSKDPIDVNY794 EKLKTDIKVV804 DRDSEEAEII814 RKYVKNTHAT824 THNAYDLEVI 834 DIFKIEREGE844 CQRYKPFKQL854 HNRRLLWHGS864 RTTNFAGILS874 QGLRIAPPEA 884 PVTGYMFGKG894 IYFADMVSKS904 ANYCHTSQGD914 PIGLILLGEV924 ALGNMYELKH 934 ASHISKLPKG944 KHSVKGLGKT954 TPDPSANISL964 DGVDVPLGTG974 ISSGVNDTSL 984 LYNEYIVYDI994 AQVNLKYLLK1004 LKFNFK
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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 | Dissecting the molecular determinants of clinical PARP1 inhibitor selectivity for tankyrase1. J Biol Chem. 2021 Jan-Jun;296:100251. | ||||
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