Mammalian ADP-ribosyltransferases and ADP-ribosylhydrolases.
ADP-ribosyltransferases (ARTs) and ADP-ribosylhydrolases (ARHs) catalyze opposing reactions, which are termed ADP-ribosylation and de-ADP-ribosylation. ARTs transfer the ADP-ribose unit from NAD (nicotinamide adenine dinucleotide) onto an acceptor, while ARHs release the ADP-ribose from the target. Like protein phosphorylation, ADP-ribosylation is a posttranslational modification regulating protein function. In many cases, ADP-ribosylation inactivates the target protein. Numerous bacterial toxins intoxicate cells by attaching an ADP-ribose moiety to a functionally important amino acid residue, thereby blocking the interaction of the target protein with other proteins. In other cases, ADP-ribosylation activates protein function. On the surface of T cells, ART2.2 ADP-ribosylates the P2X7 purinoceptor on arginine 125, thereby gating the P2X7 ion channel by presenting a ligand to its nucleotide-binding site. ADP-ribosylation is not limited to protein targets and ARTs have been described that ADP-ribosylate DNA, RNA, and small molecules. Mammalian cells express distinct families of ARTs and ARHs. Recently, molecular cloning, site directed mutagenesis and three-dimensional structural analyses of prototype mammalian ARTs and ARHs have shed fresh insight into the structure and function of these intriguing enzymes.
Institute of Immunology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany. nolte@uke.de
Friedrich
F
Koch-Nolte
Stefan
S
Kernstock
Christoph
C
Mueller-Dieckmann
Manfred S
MS
Weiss
Friedrich
F
Haag
D036002:ADP Ribose Transferases / Q000187:drug effects / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D018407:Bacterial Physiological Phenomena; D004167:Diphtheria Toxin / Q000633:toxicity; D006801:Humans; D008322:Mammals; D009699:N-Glycosyl Hydrolases / Q000187:drug effects / Q000378:metabolism*; D009586:Nitrogen Fixation
D004167:Diphtheria Toxin; D000244:Adenosine Diphosphate; D036002:ADP Ribose Transferases; D009699:N-Glycosyl Hydrolases