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 MK-4827 Ligand Info
Canonical SMILES C1CC(CNC1)C2=CC=C(C=C2)N3C=C4C=CC=C(C4=N3)C(=O)N
InChI 1S/C19H20N4O/c20-19(24)17-5-1-3-15-12-23(22-18(15)17)16-8-6-13(7-9-16)14-4-2-10-21-11-14/h1,3,5-9,12,14,21H,2,4,10-11H2,(H2,20,24)/t14-/m1/s1
InChIKey PCHKPVIQAHNQLW-CQSZACIVSA-N
PubChem Compound ID 24958200
Drug Binding Sites of Target  Top
PDB ID: 4R6E      Human artd1 (parp1) - catalytic domain in complex with inhibitor niraparib
Method X-ray diffraction Resolution 2.20 Å Mutation Yes [1]
PDB Sequence
MKSKLPKPVQ
670
DLIKMIFDVE
680
SMKKAMVEYE
690
IDLQKMPLGK
700
LSKRQIQAAY
710

SILSEVQQAV
720
SQGSSDSQIL
730
DLSNRFYTLI
740
PHDFGMKKPP
750
LLNNADSVQA
760

KAEMLDNLLD
770
IEVAYSLLRG
780
GSDDSSKDPI
790
DVNYEKLKTD
800
IKVVDRDSEE
810

AEIIRKYVKN
820
THATTHNAYD
830
LEVIDIFKIE
840
REGECQRYKP
850
FKQLHNRRLL
860

WHGSRTTNFA
870
GILSQGLRIA
880
PPEAPVTGYM
890
FGKGIYFADM
900
VSKSANYCHT
910

SQGDPIGLIL
920
LGEVALGNMY
930
ELKHASHISK
940
LPKGKHSVKG
950
LGKTTPDPSA
960

NISLDGVDVP
970
LGTGISSGVN
980
DTSLLYNEYI
990
VYDIAQVNLK
1000
YLLKLKFNFK
1010
Residue
Distance (Å)
GLN759
4.011
ALA762
3.874
GLU763
3.931
ASP766
2.682
TRP861
4.118
HIS862
3.456
GLY863
2.856
GLY888
3.644
Residue
Distance (Å)
TYR889
3.016
TYR896
3.383
PHE897
3.574
ALA898
3.839
LYS903
3.804
SER904
2.767
TYR907
3.405
GLU988
3.815
PDB ID: 7KK5      Structure of the catalytic domain of PARP1 in complex with niraparib
Method X-ray diffraction Resolution 1.70 Å Mutation No [2]
PDB Sequence
KSKLPKPVQD
671
LIKMIFDVES
681
MKKAMVEYEI
691
DLQKMPLGKL
701
SKRQIQAAYS
711

ILSEVQQAVS
721
QDSQILDLSN
734
RFYTLIPHDF
744
GKPPLLNNAD
756
SVQAKVEMLD
766

NLLDIEVAYS
776
LLRGSKDPID
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
LLKLKFNFK
Residue
Distance (Å)
GLN759
3.499
VAL762
3.786
GLU763
4.317
ASP766
2.792
TRP861
4.074
HIS862
3.325
GLY863
2.848
GLY888
3.327
Residue
Distance (Å)
TYR889
3.318
TYR896
3.313
PHE897
3.633
ALA898
3.882
LYS903
3.899
SER904
2.766
TYR907
3.399
GLU988
3.835
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 Dissecting the molecular determinants of clinical PARP1 inhibitor selectivity for tankyrase1. J Biol Chem. 2021 Jan-Jun;296:100251.

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