› 4oqa

X-ray diffraction
3.65Å resolution

Structure of Human PARP-1 bound to a DNA double strand break in complex with (2Z)-2-(2,4-dihydroxybenzylidene)-3-oxo-2,3-dihydro-1-benzofuran-7-carboxamide

Released:
DOI: 10.2210/pdb4oqa/pdb
PDB entry 4oqa coloured by chain, front view.
PDB entry 4oqa coloured by chain, side view.
PDB entry 4oqa coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery and structure-activity relationship of novel 2,3-dihydrobenzofuran-7-carboxamide and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide derivatives as poly(ADP-ribose)polymerase-1 inhibitors.
Patel MR, Bhatt A, Steffen JD, Chergui A, Murai J, Pommier Y, Pascal JM, Trombetta LD, Fronczek FR, Talele TT
OpenAccess logo J Med Chem 57 5579-601 (2014)
PMID: 24922587

Function and Biology Details

Reaction catalysed: 
NAD(+) + (ADP-D-ribosyl)(n)-acceptor = nicotinamide + (ADP-D-ribosyl)(n+1)-acceptor
Biochemical function:
Biological process:
  • not assigned
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
hetero tetramer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-117932 (preferred)
Entry contents:
2 distinct polypeptide molecules
1 distinct DNA molecule
Macromolecules (3 distinct):
Poly [ADP-ribose] polymerase 1, processed C-terminus Chains: A, D
Molecule details ›
Chains: A, D
Length: 267 amino acids
Theoretical weight: 30.52 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P09874 (Residues: 1-97, 207-366; Coverage: 25%)
Gene names: ADPRT, PARP1, PPOL
Sequence domains:
Structure domains: Zinc finger, PARP-type
Poly [ADP-ribose] polymerase 1, processed C-terminus Chains: C, F
Molecule details ›
Chains: C, F
Length: 505 amino acids
Theoretical weight: 57.04 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P09874 (Residues: 518-1014; Coverage: 49%)
Gene names: ADPRT, PARP1, PPOL
Sequence domains:
Structure domains:
DNA (26-MER) Chains: M, N
Molecule details ›
Chains: M, N
Length: 26 nucleotides
Theoretical weight: 7.99 KDa

Ligands and Environments

2 bound ligands:
Ligand ZN 4 x ZN
Ligand 2US 1 x 2US
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X29A
Spacegroup: P212121
Unit cell:
a: 65.16Å b: 114.23Å c: 294.24Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.3 0.298 0.334
Expression system: Escherichia coli

Quick links

Citations

5 review citations

PARP1: Structural insights and pharmacological targets for inhibition.
Spiegel et al. (2021)
4 more

2 mentions without citation

Rational discovery of dual-indication multi-target PDE/Kinase inhibitor for precision anti-cancer therapy using structural systems pharmacology.
Lim et al. (2019)
1 more