STRUCTURE OF THE CATALYTIC FRAGMENT OF POLY(ADP-RIBOSE) POLYMERASE FROM CHICKEN

The crystal structures of the catalytic fragment of chicken poly(ADP-r ibose) polymerase [NAD(+) ADP-ribosyltransferase; (+):poly(adenosine-d iphosphate-D-ribosyl)-acceptor ADP-D-ribosyltransferase, EC 2.4.2.30] with and without a nicotinamide-analogue inhibitor have been elucidate d. Because this enzyme is involved in the regulation of DNA repair, it s inhibitors are of interest for cancer therapy, The inhibitor shows t he nicotinamide site and also suggests the adenosine site. The enzyme is structurally related to bacterial ADP-ribosylating toxins but conta ins an additional alpha-helical domain that is suggested to relay the activation signal issued on binding to damaged DNA.