Target Binding Site Detail

Content Navigation (  All   None )                                      
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 Rucaparib Ligand Info
Canonical SMILES CNCC1=CC=C(C=C1)C2=C3CCNC(=O)C4=C3C(=CC(=C4)F)N2
InChI 1S/C19H18FN3O/c1-21-10-11-2-4-12(5-3-11)18-14-6-7-22-19(24)15-8-13(20)9-16(23-18)17(14)15/h2-5,8-9,21,23H,6-7,10H2,1H3,(H,22,24)
InChIKey HMABYWSNWIZPAG-UHFFFAOYSA-N
PubChem Compound ID 9931954
Drug Binding Sites of Target  Top
PDB ID: 6VKK      Crystal Structure of human PARP-1 CAT domain bound to inhibitor rucaparib
Method X-ray diffraction Resolution 2.10 Å Mutation Yes [1]
PDB Sequence
KSKLPKPVQD
671
LIKMIFDVES
681
MKKAMVEYEI
691
DLQKMPLGKL
701
SKRQIQAAYS
711

ILSEVQQAVS
721
QGSSDSQILD
731
LSNRFYTLIP
741
HDFGMKKPPL
751
LNNADSVQAK
761

AEMLDNLLDI
771
EVAYSLLRGS
786
KDPIDVNYEK
796
LKTDIKVVDR
806
DSEEAEIIRK
816

YVKNTHATTH
826
NAYDLEVIDI
836
FKIEREGECQ
846
RYKPFKQLHN
856
RRLLWHGSRT
866

TNFAGILSQG
876
LRIAPPEAPV
886
TGYMFGKGIY
896
FADMVSKSAN
906
YCHTSQGDPI
916

GLILLGEVAL
926
GNMYELKHAS
936
HISKLPKGKH
946
SVKGLGKTTP
956
DPSANISLDG
966

VDVPLGTGIS
976
SGVNDTSLLY
986
NEYIVYDIAQ
996
VNLKYLLKLK
1006
FNFKT
Residue
Distance (Å)
GLN759
4.080
GLU763
2.768
ASP766
3.484
TRP861
4.208
HIS862
3.327
GLY863
2.829
THR887
4.123
GLY888
3.210
TYR889
3.371
Residue
Distance (Å)
TYR896
3.438
PHE897
3.038
ALA898
3.255
LYS903
3.541
SER904
2.668
TYR907
3.387
ASN987
4.300
GLU988
3.548
PDB ID: 4RV6      Human ARTD1 (PARP1) catalytic domain in complex with inhibitor Rucaparib
Method X-ray diffraction Resolution 3.19 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
SDSKDPIDVN
793
YEKLKTDIKV
803
VDRDSEEAEI
813

IRKYVKNTHA
823
TTHNAYDLEV
833
IDIFKIEREG
843
ECQRYKPFKQ
853
LHNRRLLWHG
863

SRTTNFAGIL
873
SQGLRIAPPE
883
APVTGYMFGK
893
GIYFADMVSK
903
SANYCHTSQG
913

DPIGLILLGE
923
VALGNMYELK
933
HASHISKLPK
943
GKHSVKGLGK
953
TTPDPSANIS
963

LDGVDVPLGT
973
GISSGVNDTS
983
LLYNEYIVYD
993
IAQVNLKYLL
1003
KLKFNFK
Residue
Distance (Å)
GLN759
3.563
ALA762
4.761
GLU763
3.090
ASP766
4.467
TRP861
4.353
HIS862
3.337
GLY863
2.783
SER864
4.993
THR887
3.896
GLY888
3.987
TYR889
3.873
Residue
Distance (Å)
MET890
4.995
TYR896
3.270
PHE897
2.806
ALA898
3.385
LYS903
3.795
SER904
2.807
TYR907
3.574
ASN987
4.796
GLU988
3.437
TYR989
4.859
References  Top
REF 1 Structural basis for allosteric PARP-1 retention on DNA breaks. Science. 2020 Apr 3;368(6486):eaax6367.
REF 2 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.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.