Structure of the catalytic fragment of poly(AD-ribose) polymerase from chicken.
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.
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Institut für Organische Chemie und Biochemie, Freiburg im Breisgau, Germany.
Mennissier de Murcia
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de Murcia
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G
Schulz
G E
GE
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002645:Chickens; D018360:Crystallography, X-Ray; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism*; D010446:Peptide Fragments / Q000096:biosynthesis / Q000737:chemistry*; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D018411:Spodoptera; D014162:Transfection
D010446:Peptide Fragments; D011994:Recombinant Proteins; D009243:NAD; D011065:Poly(ADP-ribose) Polymerases