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Query: UNIPROT:P06889 (Mol)
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The amino acid sequences of several bacterial toxin ADP-ribosyltransferases, rabbit skeletal muscle transferases, and RT6.2, a rat T-cell NAD glycohydrolase, contain three separate regions of similarity, which can be aligned. Region I contains a critical histidine or arginine residue, region II, a group of closely spaced aromatic amino acids, and region III, an active-site glutamate which is at times seen as part of an acidic amino acid-rich sequence. In some of the bacterial ADP-ribosyltransferases, the nicotinamide moiety of NAD has been photo-crosslinked to this glutamate, consistent with its position in the active site. The similarities within these three regions, despite an absence of overall sequence similarity among the several transferases, are consistent with a common structure involved in NAD binding and ADP-ribose transfer.
Mol Cell Biochem 1994 Sep
PMID:Common structure of the catalytic sites of mammalian and bacterial toxin ADP-ribosyltransferases. 789 62

Numerous metabolic pathways generate free ADP-ribose at many locations within cells. The metabolic fates of this nucleotide are poorly understood and measurement of it in situ is technically difficult at present. Yet considerable evidence has accumulated implicating that protein glycation by ADP-ribose can occur. This evidence is reviewed here along with recent developments in characterizing the chemistry of this reaction and the application of this information to the identification of this posttranslational modification in protein in situ.
Mol Cell Biochem 1994 Sep
PMID:Glycation of proteins by ADP-ribose. 789 65

Mono-ADP-ribosylation is a protein modification that occurs at a number of different amino acids, dictated by the specificity of the individual ADP-ribosyltransferases. A specific cysteine in several guanine nucleotide-binding regulatory proteins is ADP-ribosylated by the bacterial protein pertussis toxin. Recent purification of an ADP-ribosylcysteine hydrolase and NAD:cysteine ADP-ribosyltransferase, and detection of ADP-ribose-cysteine linkages in tissue samples has raised hope that an endogenous regulatory cysteine-specific ADP-ribosylation pathway exists. A current goal is the identification of such a pathway for ADP-ribosylation of cysteine within animal cells. Interpretation of the data in this field has been complicated by recent reports that revealed several unforeseen chemical reactions of NAD and its metabolites with free cysteine and cysteine in proteins. This mini-review covers the latest understanding of the ADP-ribosylation reactions associated with cysteine, and provides a set of criteria for future research to establish positively the existence of an endogenous cysteine-specific mono-ADP-ribosyltransferase.
Mol Cell Biochem 1994 Sep
PMID:Enzymatic and nonenzymatic ADP-ribosylation of cysteine. 789 67

Mobilization of Ca+2 from intracellular stores is a signalling mechanism that is of fundamental importance to many cellular processes. It is mediated by two major mechanisms, the inositol 1,4,5-trisphosphate pathway and the Ca+2-induced Ca+2 release process. A naturally occurring metabolite of NAD+ called cyclic ADP-ribose has been discovered recently and shown to be as effective as inositol 1,4,5-trisphosphate in mobilizing Ca+2 stores in sea urchin eggs, a marine invertebrate cell, as well as several mammalian cells. This article reviews the accumulating evidence that indicates cyclic ADP-ribose may function as a physiological regulator of the Ca+2-induced Ca+2 release process and the current knowledge about its receptor as well as the enzymes involved in its metabolism.
Mol Cell Biochem 1994 Sep
PMID:Cyclic ADP-ribose: a calcium mobilizing metabolite of NAD+. 789 68

NAD glycohydrolases are the longest known enzymes that catalyze ADP-ribose transfer. The function of these ubiquitous, membrane-bound enzymes has been a long standing puzzle. The NAD glycohydrolases are briefly reviewed in light of the discovery by our laboratory that NAD glycohydrolases are bifunctional enzymes that can catalyze both the synthesis and hydrolysis of cyclic ADP-ribose, a putative second messenger of calcium homeostasis.
Mol Cell Biochem 1994 Sep
PMID:NAD glycohydrolases: a possible function in calcium homeostasis. 789 69

Poly(ADP-ribose) polymerase cDNAs have been isolated from different classes of animals. Cloning of genes from lower eukaryotes has allowed us to investigate directly the biological functions of poly(ADP-ribosyl)ation in vivo. The conservation of specific regions among mammals, chicken, Xenopus laevis, and Drosophila melanogaster reveals the essential structural elements required for recognition of breaks in DNA and for catalytic activity. Cys, His and basic residues in the zinc-finger consensus region are conserved. The carboxyl terminal region corresponding to an NAD-binding domain is strongly conserved. The dinucleotide-binding consensus sequence and beta 1-alpha A-beta 2, Rossmann fold structure, and beta-sheet structures are completely conserved from mammals to insect. In Drosophila, a putative leucine-zipper motif has been identified, and other poly(ADP-ribose) polymerases also contain an alpha-helical, amphipathic structure in the auto-modification domain. In this article, we review the recent structural analyses of the functional domains of poly(ADP-ribose) polymerase in phylogenetically divergent species, and discuss the implications of structural conservation for its biological functions.
Mol Cell Biochem 1994 Sep
PMID:Poly(ADP-ribose) polymerase: structural conservation among different classes of animals and its implications. 789 71

Poly(ADP-ribose) catabolism is a complex situation involving many proteins and DNA. We have developed an in vitro turnover system where poly(ADP-ribose) metabolism is monitored in presence of different relative amounts of two principal enzymes poly(ADP-ribose) transferase and poly(ADP-ribose) glycohydrolase along with other proteins and DNA. Our current results reviewed here show that the quality of polymer, i.e. chain length and complexity, as well as preference for the nuclear substrate varies depending upon the availability of poly(ADP-ribose) glycohydrolase. These results are interpreted in the light of the recent data implicating poly(ADP-ribose) metabolism in DNA-repair.
Mol Cell Biochem 1994 Sep
PMID:Poly(ADP-ribose) catabolism in mammalian cells. 789 74

The early historical background of the discovery of poly(ADP-ribose) and the following development of science on poly(ADP-ribose) are reviewed. Fundamental knowledge on the natures of poly(ADP-ribose), poly(ADP-ribose) polymerase and enzymes degrading poly(ADP-ribose) are summarized with brief description on the methodology for their purification and characterization. Future prospect of research on biological significance of poly(ADP-ribose) has also been discussed briefly.
Mol Cell Biochem 1994 Sep
PMID:Poly(ADP-ribose): historical perspective. 789 75

The enzymes poly(ADP-ribose)polymerase and poly(ADP-ribose) glycohydrolase may cooperate to drive a histone shuttle mechanism in chromatin. The mechanism is triggered by binding of the N-terminal zinc-finger domain of the polymerase to DNA strand breaks, which activates the catalytic activities residing in the C-terminal domain. The polymerase converts into a protein carrying multiple ADP-ribose polymers which displace histones from DNA by specifically targeting the histone tails responsible for DNA condensation. As a result, the domains surrounding DNA strand breaks become accessible to other proteins. Poly(ADP-ribose)glycohydrolase attacks ADP-ribose polymers in a specific order and thereby releases histones for reassociation with DNA. Increasing evidence from different model systems suggests that histone shuttling participates in DNA repair in vivo as a catalyst for nucleosomal unfolding.
Mol Cell Biochem 1994 Sep
PMID:Histone shuttling by poly ADP-ribosylation. 789 76

Poly (ADP-ribose) polymerase has an obligatory requirement for DNA strand-breaks in order to show full enzyme activity. Exposure of cells to DNA damaging agents activates this enzyme presumably through the production of DNA strand-breaks, either directly or via cellular enzymes. Recent evidence from manipulations of the cloned cDNA of this enzyme confirm the earlier evidence, obtained using enzyme inhibitors, that this enzyme is involved in DNA excision repair, probably at or near the ligation step. A very unusual human genetic disease has provided direct evidence for a link between the enzyme activities of poly (ADP-ribose) polymerase and of DNA ligase I. There is also some evidence that this enzyme may be involved in other cases of DNA breakage and rejoining, such as homologous and non-homologous DNA recombination, for example, in sister chromatid exchanges, in DNA transfection, in the integration of retroviral proviral DNA and in variable antigen switching in African trypanosomes.
Mol Cell Biochem 1994 Sep
PMID:The function of poly (ADP-ribosylation) in DNA breakage and rejoining. 789 78


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