Mono-ADP-ribosylation: a reversible posttranslational modification of proteins.
Mono-ADP-ribosyltransferase activity has been detected in numerous vertebrate tissues and transferase cDNAs from a few species have recently been cloned. In vitro ADP-ribosylation has been demonstrated with diverse substrates such as phosphorylase kinase, actin, and Gs alpha resulting in the alteration of substrate function. ADP-ribosylation of endogenous target proteins has been observed in chicken heterophils, rat brain, and human platelets, and integrin alpha 7 was found to be the endogenous substrate of the GPI-anchored rabbit skeletal muscle transferase. The reversibility of ADP-ribosylation is made possible by ADP-ribosylarginine hydrolases which have been isolated and cloned from rodent and human tissues. The transferases and hydrolases could in principle form an intracellular ADP-ribosylation regulatory cycle. In the case of the skeletal muscle transferases, however, processing of ADP-ribosylated integrin alpha 7 is carried out by phosphodiesterases and possibly phosphatases (Fig. 1). Most bacterial toxin and eukaryotic mono-ADP-ribosyltransferases, and perhaps other NAD-utilizing enzymes such as the RT6 family of proteins, share a common catalytic-site structure despite a lack of overall sequence identity. The transferases that have been studied thus far possess a critical glutamic acid and other amino acids at the catalytic cleft which function to position NAD for nucleophilic attack at the N-glycosidic linkage for either ADP-ribose transfer or NAD hydrolysis. The amino acid differences among transferases at the active site may reflect different catalytic mechanisms of ADP-ribosylation or may be required for accommodating the different ADP-ribose acceptor molecules.
Okazaki
I J
IJ
Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Moss
J
J
D036002:ADP Ribose Transferases / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000595:Amino Acid Sequence; D008969:Molecular Sequence Data
D036002:ADP Ribose Transferases