› 4opx

X-ray diffraction
3.31Å resolution

Structure of Human PARP-1 bound to a DNA double strand break in complex with (2R)-5-fluoro-2-methyl-2,3-dihydro-1-benzofuran-7-carboxamide

Released:
DOI: 10.2210/pdb4opx/pdb
PDB entry 4opx coloured by chain, front view.
PDB entry 4opx coloured by chain, side view.
PDB entry 4opx 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
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-117931 (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 2UR 1 x 2UR
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X29A
Spacegroup: P212121
Unit cell:
a: 65.15Å b: 112.91Å c: 295.29Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.304 0.303 0.325
Expression system: Escherichia coli

Quick links

Citations

5 review citations

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

3 mentions without citation

Comparative inhibitory profile and distribution of bacterial PARPs, using Clostridioides difficile CD160 PARP as a model.
García-Saura et al. (2018)
2 more