4GV2: Human Artd3 (parp3) - Catalytic Domain In Complex With Inhibitor Me0354

Citation:
Abstract
Inhibiting ADP-ribosyl transferases with PARP-inhibitors is considered a promising strategy for the treatment of many cancers and ischemia, but most of the cellular targets are poorly characterized. Here, we describe an inhibitor of ADP-ribosyltransferase-3/poly(ADP-ribose) polymerase-3 (ARTD3), a regulator of DNA repair and mitotic progression. In vitro profiling against 12 members of the enzyme family suggests selectivity for ARTD3, and crystal structures illustrate the molecular basis for inhibitor selectivity. The compound is active in cells, where it elicits ARTD3-specific effects at submicromolar concentration. Our results show that by targeting the nicotinamide binding site, selective inhibition can be achieved among the closest relatives of the validated clinical target, ADP-ribosyltransferase-1/poly(ADP-ribose) polymerase-1.
PDB ID: 4GV2Download
MMDB ID: 111055
PDB Deposition Date: 2012/8/30
Updated in MMDB: 2013/10
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 4GV2: monomeric; determined by author and by software (PISA)
Molecular Components in 4GV2
Label Count Molecule
Protein (1 molecule)
1
Poly [adp-ribose] Polymerase 3(Gene symbol: PARP3)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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