Structure of PDB 5a00 Chain A Binding Site BS01

Receptor Information
>5a00 Chain A (length=340) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
KSKLPKPVQDLIKMIFDVESMKKAMVEYEIDLQKMPLGKLSKRQIQAAYS
ILSEVQQAVSQGSSDSQILDLSNRFYTLIPHDPPLLNNADSVQAKVEMLD
NLLDIEVAYSLLRGGSKDPIDVNYEKLKTDIKVVDRDSEEAEIIRKYVKN
THATTHNAYDLEVIDIFKIEREGECQRYKPFKQLHNRRLLWHGSRTTNFA
GILSQGLRIAPPEAPVTGYMFGKGIYFADMVSKSANYCHTSQGDPIGLIL
LGEVALGNMYELKHASHISKLPKGKHSVKGLGKTTPDPSANISLDGVDVP
LGTGISSGVNDTSLLYNEYIVYDIAQVNLKYLLKLKFNFK
Ligand information
Ligand IDD7N
InChIInChI=1S/C20H24F3N3O2/c21-13-9-12-11-26(19(28)17(12)16(10-13)18(24)27)15-3-7-25(8-4-15)14-1-5-20(22,23)6-2-14/h9-10,14-15H,1-8,11H2,(H2,24,27)
InChIKeyARYVAQSYRLZVQD-UHFFFAOYSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6c1c(cc(c2c1CN(C2=O)C3CCN(CC3)C4CCC(CC4)(F)F)C(=O)N)F
CACTVS 3.385NC(=O)c1cc(F)cc2CN(C3CCN(CC3)C4CCC(F)(F)CC4)C(=O)c12
FormulaC20 H24 F3 N3 O2
Name2-[1-(4,4-Difluorocyclohexyl)-piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide
ChEMBLCHEMBL3606021
DrugBank
ZINCZINC000068248918
PDB chain5a00 Chain A Residue 2012 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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PDB5a00 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.
Resolution2.75 Å
Binding residue
(original residue number in PDB)		Q759 V762 H862 G863 Y889 Y896 F897 A898 K903 S904 Y907
Binding residue
(residue number reindexed from 1)		Q93 V96 H192 G193 Y219 Y226 F227 A228 K233 S234 Y237
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=7.52,Kd<0.03uM
BindingDB: Kd=8.6nM,IC50=40nM
Enzymatic activity
Catalytic site (original residue number in PDB) S904 Y907 E988
Catalytic site (residue number reindexed from 1) S234 Y237 E318
Enzyme Commision number 2.4.2.-
2.4.2.30: NAD(+) ADP-ribosyltransferase.
Gene Ontology
Molecular Function
GO:0003950 NAD+-protein poly-ADP-ribosyltransferase activity

View graph for
Molecular Function
External links
PDB RCSB:5a00, PDBe:5a00, PDBj:5a00
PDBsum5a00
PubMed26222319
UniProtP09874|PARP1_HUMAN Poly [ADP-ribose] polymerase 1 (Gene Name=PARP1)

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