ADP-Ribosylation in Animal Tissues: Structure, Function, and Biology of Mono (ADP-ribosyl) Transferases and Related Enzymes

Although ADP-ribosylation has been known as a post-translational modification of proteins for approximately thirty years, the study of endogenous mono-ADP-ribosylation in animal tissues has remained somewhat of an orphan field during this time. Until recently, interest in the field has concentrated on two types of phenomena: (I) poly-ADP-ribosylation of nuclear proteins in eukaryotes as a mechanism possibly involved in DNA excision repair and (2) mono-ADP-ribosylation by bacterial enzymes, either as a toxic mechanism in eukaryotic host cells or as a reversible regulatory mechanism for control of nitrogen fixation. The identification of diphtheria, cholera, and pertussis toxins as mono(ADP-ribosyl)transferases and their subsequent purification and crystallization have shaped our current knowledge of the biology of mono-ADP-ribosylation reactions and the structure-function relationships of the enzymes involved. In contrast, endogenous transferases of animal tissues escaped molecular cloning, and for a long time their biological relevance was merely postulated by analogy to their bacterial cousins.