Structure of PDB 6bhv Chain A Binding Site BS01

Receptor Information

>6bhv Chain A (length=238) Species: 9606 (Homo sapiens)

SKLPKPVQDLIKMIFGPIDVNYEKLKTDIKVVDRDSEEAEIIRKYVKNTH
ATTHNAYDLEVIDIFKIEREGECQRYKPFKQLHNRRLLWHGSRTTNFAGI
LSQGLRIAPPEAPVTGYMFGKGIYFADMVSKSANYCHTSQGDPIGLILLG
EVALGNMYELKHASHISKLPKGKHSVKGLGKTTPDPSANISLDGVDVPLG
TGISSGVNDTSLLYNEYIVYDIAQVNLKYLLKLKFNFK

Ligand information

• Ligand ID: DQV
• InChI: InChI=1S/C22H28N6O14P2/c23-19-13-21(26-7-25-19)28(8-27-13)22-17(32)15(30)12(41-22)6-39-44(36,37)42-43(34,35)38-5-11-14(29)16(31)18(40-11)9-2-1-3-10(4-9)20(24)33/h1-4,7-8,11-12,14-18,22,29-32H,5-6H2,(H2,24,33)(H,34,35)(H,36,37)(H2,23,25,26)/t11-,12-,14-,15-,16-,17-,18+,22-/m1/s1
• InChIKey: HNKKJJHKTPALEK-RACQCECLSA-N
• SMILES:
  ACDLabs 12.01: O=P(O)(OP(O)(=O)OCC3OC(n1cnc2c1ncnc2N)C(C3O)O)OCC5C(O)C(C(c4cccc(c4)C(=O)N)O5)O
  OpenEye OEToolkits 2.0.6: c1cc(cc(c1)C(=O)N)[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=O)(O)OP(=O)(O)OC[C@@H]3[C@H]([C@H]([C@@H](O3)n4cnc5c4ncnc5N)O)O)O)O
  OpenEye OEToolkits 2.0.6: c1cc(cc(c1)C(=O)N)C2C(C(C(O2)COP(=O)(O)OP(=O)(O)OCC3C(C(C(O3)n4cnc5c4ncnc5N)O)O)O)O
  CACTVS 3.385: NC(=O)c1cccc(c1)[C@@H]2O[C@H](CO[P](O)(=O)O[P](O)(=O)OC[C@H]3O[C@H]([C@H](O)[C@@H]3O)n4cnc5c(N)ncnc45)[C@@H](O)[C@H]2O
  CACTVS 3.385: NC(=O)c1cccc(c1)[CH]2O[CH](CO[P](O)(=O)O[P](O)(=O)OC[CH]3O[CH]([CH](O)[CH]3O)n4cnc5c(N)ncnc45)[CH](O)[CH]2O
• Formula: C22 H28 N6 O14 P2
• Name: [(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl [(2R,3S,4R,5S)-5-(3-carbamoylphenyl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl dihydrogen diphosphate (non-preferred name)
• ChEMBL: CHEMBL233434
• ZINC: ZINC000049946796
• PDB chain: 6bhv Chain A Residue 1101

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6bhv NAD+analog reveals PARP-1 substrate-blocking mechanism and allosteric communication from catalytic center to DNA-binding domains.
• Resolution: 2.3 Å
• Binding residue (original residue number in PDB): H862 G863 S864 N868 G871 I872 L877 R878 Y889 M890 Y896 F897 S904 Y907 E988
• Binding residue (residue number reindexed from 1): H90 G91 S92 N96 G99 I100 L105 R106 Y117 M118 Y124 F125 S132 Y135 E216
• Annotation score: 3
• Binding affinity: MOAD: Kd=5.87uM
  PDBbind-CN: -logKd/Ki=5.23,Kd=5.87uM

Enzymatic activity

• Catalytic site (original residue number in PDB): S904 Y907 E988
• Catalytic site (residue number reindexed from 1): S132 Y135 E216
• 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

External links

• PDB: RCSB:6bhv, PDBe:6bhv, PDBj:6bhv
• PDBsum: 6bhv
• PubMed: 29487285
• UniProt: P09874|PARP1_HUMAN Poly [ADP-ribose] polymerase 1 (Gene Name=PARP1)