Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
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
PARP1_HUMAN
Ligand General Information  Top
Ligand Name EB-47 Ligand Info
Canonical SMILES C1CN(CCN1CC(=O)NC2=CC=CC3=C2CNC3=O)C(=O)C4C(C(C(O4)N5C=NC6=C(N=CN=C65)N)O)O
InChI 1S/C24H27N9O6/c25-20-16-21(28-10-27-20)33(11-29-16)24-18(36)17(35)19(39-24)23(38)32-6-4-31(5-7-32)9-15(34)30-14-3-1-2-12-13(14)8-26-22(12)37/h1-3,10-11,17-19,24,35-36H,4-9H2,(H,26,37)(H,30,34)(H2,25,27,28)/t17-,18+,19-,24+/m0/s1
InChIKey DDFLFKTXUWPNMV-UAKAABGRSA-N
PubChem Compound ID 9871899
Drug Binding Sites of Target  Top
PDB ID: 6VKQ      Crystal Structure of human PARP-1 CAT domain bound to inhibitor EB-47
Method X-ray diffraction Resolution 2.90 Å Mutation Yes [1]
PDB Sequence
KLPKPVQDLI
673
KMIFDVESMK
683
KAMVEYEIDL
693
QKMPLGKLSK
703
RQIQAAYSIL
713

SEVQQAVSQG
723
SSDSQILDLS
733
NRFYTLIPHD
743
FGMKKPPLLN
753
NADSVQAKAE
763

MLDNLLDIEV
773
AYSLLRGGID
791
VNYEKLKTDI
801
KVVDRDSEEA
811
EIIRKYVKNT
821

HATTHNAYDL
831
EVIDIFKIER
841
EGECQRYKPF
851
KQLHNRRLLW
861
HGSRTTNFAG
871

ILSQGLRIAP
881
PEAPVTGYMF
891
GKGIYFADMV
901
SKSANYCHTS
911
QGDPIGLILL
921

GEVALGNMYE
931
LKHASHISKL
941
PKGKHSVKGL
951
GKTTPDPSAN
961
ISLDGVDVPL
971

GTGISSGVND
981
TSLLYNEYIV
991
YDIAQVNLKY
1001
LLKLKFNFKT
1011
Residue
Distance (Å)
ASP766
3.644
LEU769
3.366
ASP770
3.588
TRP861
4.136
HIS862
3.350
GLY863
2.898
SER864
2.590
ASN868
3.424
GLY871
4.260
ILE872
3.534
GLN875
3.363
GLY876
2.985
Residue
Distance (Å)
LEU877
3.655
ARG878
3.355
ALA880
4.712
GLY888
3.906
TYR889
3.142
TYR896
3.084
PHE897
3.673
ALA898
4.320
LYS903
4.160
SER904
2.632
TYR907
3.522
GLU988
3.686
PDB ID: 7AAB      Crystal structure of the catalytic domain of human PARP1 in complex with inhibitor EB-47
Method X-ray diffraction Resolution 2.80 Å Mutation Yes [2]
PDB Sequence
KSKLPKPVQD
671
LIKMIFDVES
681
MKKAMVEYEI
691
DLQKMPLGKL
701
SKRQIQAAYS
711

ILSEVQQAVS
721
QGSSDSQILD
731
LSNRFYTLIP
741
HDFGMKKPPL
751
LNNADSVQAK
761

AEMLDNLLDI
771
EVAYSLLRGG
781
SDDSSKDPID
791
VNYEKLKTDI
801
KVVDRDSEEA
811

EIIRKYVKNT
821
HATTHNAYDL
831
EVIDIFKIER
841
EGECQRYKPF
851
KQLHNRRLLW
861

HGSRTTNFAG
871
ILSQGLRIAP
881
PEAPVTGYMF
891
GKGIYFADMV
901
SKSANYCHTS
911

QGDPIGLILL
921
GEVALGNMYE
931
LKHASHISKL
941
PKGKHSVKGL
951
GKTTPDPSAN
961

ISLDGVDVPL
971
GTGISSGVND
981
TSLLYNEYIV
991
YDIAQVNLKY
1001
LLKLKFNFKT
1011
Residue
Distance (Å)
ASP766
3.853
ASP770
3.276
TRP861
3.956
HIS862
2.790
GLY863
2.961
SER864
2.732
ASN868
3.343
GLY871
3.338
ILE872
3.419
GLN875
4.115
GLY876
2.753
Residue
Distance (Å)
LEU877
3.365
ARG878
2.890
TYR889
3.376
GLY894
4.853
TYR896
3.251
PHE897
4.249
ALA898
4.442
LYS903
3.889
SER904
2.781
TYR907
3.464
GLU988
4.090
References  Top
REF 1 Structural basis for allosteric PARP-1 retention on DNA breaks. Science. 2020 Apr 3;368(6486):eaax6367.
REF 2 Dynamics of the HD regulatory subdomain of PARP-1; substrate access and allostery in PARP activation and inhibition. Nucleic Acids Res. 2021 Feb 26;49(4):2266-2288.

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