› 4hhy

X-ray diffraction
2.36Å resolution

Crystal structure of PARP catalytic domain in complex with novel inhibitors

Released:
DOI: 10.2210/pdb4hhy/pdb
PDB entry 4hhy coloured by chain, front view.
PDB entry 4hhy coloured by chain, side view.
PDB entry 4hhy coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Design, synthesis, and biological evaluation of a series of benzo[de][1,7]naphthyridin-7(8H)-ones bearing a functionalized longer chain appendage as novel PARP1 inhibitors.
Ye N, Chen CH, Chen T, Song Z, He JX, Huan XJ, Song SS, Liu Q, Chen Y, Ding J, Xu Y, Miao ZH, Zhang A
J Med Chem 56 2885-903 (2013)
PMID: 23473053

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:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-140785 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Poly [ADP-ribose] polymerase 1, processed C-terminus Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 355 amino acids
Theoretical weight: 39.58 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P09874 (Residues: 660-1011; Coverage: 35%)
Gene names: ADPRT, PARP1, PPOL
Sequence domains:
Structure domains:

Ligands and Environments

3 bound ligands:
Ligand 15R 4 x 15R
Ligand SO4 2 x SO4
Ligand PEG 1 x PEG
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRF BEAMLINE BL17U
Spacegroup: P212121
Unit cell:
a: 103.797Å b: 107.549Å c: 143.107Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.24 0.237 0.299
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

6 review citations

Tankyrases: structure, function and therapeutic implications in cancer.
Haikarainen et al. (2014)
5 more

5 mentions without citation

Crystal structure-based discovery of a novel synthesized PARP1 inhibitor (OL-1) with apoptosis-inducing mechanisms in triple-negative breast cancer.
Fu et al. (2016)
4 more