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Crystal structure of the catalytic domain of human PARP2 in complex with PARP inhibitor ABT-888

Karlberg, Tobias LU ; Hammarström, Martin ; Schütz, Patrick ; Svensson, Linda and Schüler, Herwig LU orcid (2010) In Biochemistry 49(6). p.8-1056
Abstract

Poly-ADP-ribose polymerases (PARPs) catalyze transfer of ADP-ribose from NAD(+) to specific residues in their substrate proteins or to growing ADP-ribose chains. PARP activity is involved in processes such as chromatin remodeling, transcription control, and DNA repair. Inhibitors of PARP activity may be useful in cancer therapy. PARP2 is the family member that is most similar to PARP1, and the two can act together as heterodimers. We used X-ray crystallography to determine two structures of the catalytic domain of human PARP2: the complexes with PARP inhibitors 3-aminobenzamide and ABT-888. These results contribute to our understanding of structural features and compound properties that can be employed to develop selective inhibitors of... (More)

Poly-ADP-ribose polymerases (PARPs) catalyze transfer of ADP-ribose from NAD(+) to specific residues in their substrate proteins or to growing ADP-ribose chains. PARP activity is involved in processes such as chromatin remodeling, transcription control, and DNA repair. Inhibitors of PARP activity may be useful in cancer therapy. PARP2 is the family member that is most similar to PARP1, and the two can act together as heterodimers. We used X-ray crystallography to determine two structures of the catalytic domain of human PARP2: the complexes with PARP inhibitors 3-aminobenzamide and ABT-888. These results contribute to our understanding of structural features and compound properties that can be employed to develop selective inhibitors of human ADP-ribosyltransferases.

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author
; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Benzamides/chemistry, Benzimidazoles/chemistry, Catalytic Domain/drug effects, Cell Cycle Proteins/chemistry, Crystallization, Crystallography, X-Ray, Glutamic Acid/chemistry, Humans, Hydrogen Bonding/drug effects, Mice, Poly (ADP-Ribose) Polymerase-1, Poly(ADP-ribose) Polymerase Inhibitors, Poly(ADP-ribose) Polymerases/chemistry, Protein Structure, Secondary/drug effects
in
Biochemistry
volume
49
issue
6
pages
3 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:20092359
  • scopus:76749153013
ISSN
0006-2960
DOI
10.1021/bi902079y
language
English
LU publication?
no
id
d4d48823-7027-43f0-ad02-b11ea7a9e3d7
date added to LUP
2024-11-21 18:01:36
date last changed
2025-04-25 22:06:54
@article{d4d48823-7027-43f0-ad02-b11ea7a9e3d7,
  abstract     = {{<p>Poly-ADP-ribose polymerases (PARPs) catalyze transfer of ADP-ribose from NAD(+) to specific residues in their substrate proteins or to growing ADP-ribose chains. PARP activity is involved in processes such as chromatin remodeling, transcription control, and DNA repair. Inhibitors of PARP activity may be useful in cancer therapy. PARP2 is the family member that is most similar to PARP1, and the two can act together as heterodimers. We used X-ray crystallography to determine two structures of the catalytic domain of human PARP2: the complexes with PARP inhibitors 3-aminobenzamide and ABT-888. These results contribute to our understanding of structural features and compound properties that can be employed to develop selective inhibitors of human ADP-ribosyltransferases.</p>}},
  author       = {{Karlberg, Tobias and Hammarström, Martin and Schütz, Patrick and Svensson, Linda and Schüler, Herwig}},
  issn         = {{0006-2960}},
  keywords     = {{Animals; Benzamides/chemistry; Benzimidazoles/chemistry; Catalytic Domain/drug effects; Cell Cycle Proteins/chemistry; Crystallization; Crystallography, X-Ray; Glutamic Acid/chemistry; Humans; Hydrogen Bonding/drug effects; Mice; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases/chemistry; Protein Structure, Secondary/drug effects}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{6}},
  pages        = {{8--1056}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Biochemistry}},
  title        = {{Crystal structure of the catalytic domain of human PARP2 in complex with PARP inhibitor ABT-888}},
  url          = {{http://dx.doi.org/10.1021/bi902079y}},
  doi          = {{10.1021/bi902079y}},
  volume       = {{49}},
  year         = {{2010}},
}