Open AccessStructure of the catalytic fragment of poly(AD-ribose) polymerase from chicken.
Author(s) -
Ruf A,
Josiane Ménissier de Murcia,
Gilbert M. de Murcia,
Georg E. Schulz
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.15.7481
Subject(s) - nad+ kinase , nicotinamide , poly adp ribose polymerase , polymerase , enzyme , ribose , chemistry , dna , biochemistry , nicotinamide adenine dinucleotide , stereochemistry , microbiology and biotechnology , adenosine diphosphate , adenosine , biology , platelet , platelet aggregation , immunology
The crystal structures of the catalytic fragment of chicken poly(ADP-ribose) polymerase [NAD+ ADP-ribosyltransferase; NAD+:poly(adenosine-diphosphate-D-ribosyl)-acceptor ADP-D-ribosyltransferase, EC 2.4.2.30] with and without a nicotinamide-analogue inhibitor have been elucidated. Because this enzyme is involved in the regulation of DNA repair, its inhibitors are of interest for cancer therapy. The inhibitor shows the nicotinamide site and also suggests the adenosine site. The enzyme is structurally related to bacterial ADP-ribosylating toxins but contains an additional alpha-helical domain that is suggested to relay the activation signal issued on binding to damaged DNA.