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Mechanisms of poly(ADP‐ribose) polymerase catalysis; mono‐ADP‐ribosylation of poly(ADP‐ribose) polymerase at nanomolar concentrations of NAD
Author(s) -
Bauer Pal I.,
Hakam Alaeddin,
Kun Ernest
Publication year - 1986
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(86)80188-0
Subject(s) - nad+ kinase , poly adp ribose polymerase , polymerase , adp ribosylation , chemistry , ribose , biochemistry , enzyme , microbiology and biotechnology , biology
Calf thymus and rat liver poly(ADP‐ribose) polymerase enzymes, and the polymerase present in extracts of rat liver nuclei synthesize unstable mono‐ADP‐ribose protein adducts at 100 nM or lower NAD concentrations. The isolated enzyme‐mono‐ADP‐ribose adduct hydrolyses to ADP‐ribose and enzyme protein at pH values slightly above 7.0 indicating a continuous release of ADP‐ribose from NAD through this enzyme‐bound intermediate under physiological conditions. NH 2 OH at pH 7.0 hydrolyses the mono‐ADP‐ribose enzyme adduct. Desamino NAD and some other homologs at nanomolar concentrations act as ‘forward’ activators of the initiating mono‐ADP‐ribosylation reaction. These NAD analogs at micromolar concentrations do not affect polymer formation that takes place at micromolar NAD concentrations. Benzamides at nanomolar concentrations also activate mono‐ADP‐ribosylation of the enzyme, but at higher concentrations inhibit elongation at micromolar NAD as substrate. In nuclei, the enzyme molecule extensively auto‐ADP‐ribosylates itself, whereas histones are trans‐ADP‐ribosylated to a much lower extent. The unstable mono‐ADP‐ribose enzyme adduct represents an initiator intermediate in poly ADP‐ribosylation.