ADP-ribosyl transferase

ADP-Ribosyl transferase (from human placenta) [9026-30-6]. Purified by making an affinity absorbent for ADP-ribosyltransferase by coupling 3-aminobenzamide to Sepharose 4B. [Burtscher et al. Anal Biochem 152 285 1986.]... 

Nucleotidylation - the addition of adenylate-residues by Lnu enzymes - can also be the cause of resistance to lincosamide antibiotics in staphylococci and enterococci. A plasmid encoded ADP-ribosylating transferase (Arr-2) that leads to rifampicin resistance has been detected in various Enterobacteriaceae as well as in Pseudomonas aeruginosa. 

Banasik M, Komura H, Shimoyama M, Ueda K (1992) Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferase. J Biol Chem 267 1569-1575... 

The sirtuins (silent information regulator 2-related proteins class III HDACs) form a specific class of histone deacetylases. First, they do not share any sequence or structural homology with the other HDACs. Second, they do not require zinc for activity, but rather use the oxidized form of nicotinamide adenine dinucleotide (NAD ) as cofactor. The reaction catalyzed by these enzymes is the conversion of histones acetylated at specific lysine residues into deacetylated histones, the other products of the reaction being nicotinamide and the metabolite 2 -0-acetyl-adenosine diphosphate ribose (OAADPR) [51, 52]. As HATs and other HDACs, sirtuins not only use acetylated histones as substrates but can also deacetylate other proteins. Intriguingly, some sirtuins do not display any deacetylase activity but act as ADP-ribosyl transferases. 

STEREOCHEMICAL TERMINOLOGY, lUPAC RECOMMENDATIONS TRANSCARBOXYLASE TRANSCRIPTION COMPLEX KINETICS TRANSCYTOSIS Transducin ADP-ribosylation, ADP-RIBOSYLATION TRANSFERASES... 

Vibrio cholera, the bacterium that causes cholera, colonizes the small intestine and produces cholera enterotoxin, which, as a consequence, brings about various symptoms including watery diarrhea. Cholera toxin is made up of a single A subunit of 27 kDa (CTA) and a nontoxic pentamer of B subunits of 11.6 kDa (CTB) together, these form a hexameric multi mer (Daniell et al., 2001). The A subunit has ADP ribosyl-transferase activity and facilitates entry of the toxin into epithelial cells. When administered... 

ADP-Ribosyl transferase (from human placenta). Purified by making an affinity absorbent for ADP-... 

PARP Poly(ADP-ribose) polymerase ADP ribosyl transferase, ADPRT1, PPOL... 

Cholera toxin is an ADP ribosyl transferase that ADPribosylates Gas-GTP, this inhibiting the Gas subunit GTP-hydrolyzing activity and thus preventing reversion to the inactive... 

Fu, Z., Fenselau, C. (2005). Proteomic evidence for roles for nucleation and poly(ADP-ribosyl)transferase in drug resistance. /. Proteome Res. 4. 

The primary cellular substrate for cholera toxin ADP-ribosyl-transferase is G a (Gill and Meren, 1978 Johnson etal., 1978 Kaslow... 

Zolkiewska A, Okosaki IJ, Moss J (1994) Vertebrate mono-ADP-ribosyl-transferases. In Mo/. Cell. Biochem. 138 107-112. 

Slama JT, Simmons AM (1989) Inhibition of NAD glycohydrolase and ADP-ribosyl transferases by carbocyclic analogues of oxidized nicotinamide adenine dinucleotide. In Biochemistry 28 7688-7693. 

Aktories, K, Braun, S, Rosener, S ef al. (1989) The rho gene product expressed in E. coli is a substrate for botulinum ADP-ribosyl transferase C3. In Biochem. Biophys. Res. Common. 158 209-13. 

Simpson LL, Stiles BG, Zepeda H etal. (1989) Production by Clostridium spiroforme of an iotalike toxin that possesses mono(ADP-ribosyl)transferase activity Identification of a novel class of ADP- ribosyltransferases. In Infect. Immun. 57 255-61 Stiles BG, Wilkens TD (1986) Purification and characterization of Clostridium perfringens iota toxin dependence on two nonlinked proteins for biological activity. In Infect. Immun. 54 683-8... 

These bonds are characteristic of the various mono(ADP-ribosyl) transferase catalyzed reactions that are known (see section on mono(ADP-ribosyl)ation reactions below). 

The best understood reactions are those catalyzed by ADP-ribosyl transferase components of certain bacterial toxins. These include, for example, toxins produced by Vibrio cholerae (the causative agent of cholera), pertussis toxin (from Bordetella pertussis, which causes whooping cough), diphtheria toxin, exotoxin A from Pseudomonas aeruginosa (an opportunistic pathogen), and toxins from Clostridium botulinum. 

Most of these toxins consist of two functional moieties, A and B. The A moiety carries the ADP-ribosyl transferase activity and the B moiety mediates cellular uptake of the toxin. All bacterial toxins so far studied, modify nucleotide-binding proteins in their target cells, and are proving to be valuable experimental tools with which to study the functions of their target proteins. Also, their use has paved the way for the discovery of ADP-ribosyl transferases in uninfected mammalian cells which may carry out similar reactions. 

Some examples illustrating current knowledge on the action of toxin ADP-ribosyl transferases are given below ... 

EF-2 + NAD —> EF-2(ADP-ribose) + nicotinamide toxin ADP-ribosyl transferase activity... 

Elongation Factor 2. Eukaryotic ADP-ribosyl transferases, which modify EF-2, have also now been isolated from a variety of animal species and tissues. The in... 

Actin. This is one of the most important components in the cytoskeletal architecture, and in the movement of cytoplasm in eukaryotic cells. In addition to muscle contraction, actin is involved in cellular processes such as phagocytosis, secretion, cell migration, and the maintenance of cell shape. A recent report shows that a mammalian cell arginine-specific ADP-ribosyl transferase can ADP-ribosylate actin molecules, suggesting that this could be a regulatory mechanism in the above cellular functions (Terashima et al., 1992). 

Mitochondrial ADP-ribosylation. Other protein substrates for mono(ADP-ribosyl) transferases continue to be reported, but the best characterized reaction is that of mammalian cell mitochondria. Most mono-ADP-ribosyl-protein conjugates in eukaryotic cells are associated with mitochondria. A specific function, namely, stimulation of calcium release from mitochondria, has been ascribed to ADP-ribosylation activity in this organelle. This could, therefore, be an important cell regulatory mechanism, since numerous calcium-dependent enzymes play an important role in cell functioning. 

The use of bacterial toxins as molecular probes will continue to provide valuable information on the functions of their various substrates. In addition, studies on endogenous cellular mono(ADP-ribosyl) transferases look set to expand. New substrates will be identified and the biochemical consequences of the different modifications will reveal the roles played by mono(ADP-ribosylation) reactions in different cell compartments. For example, the case of cytoskeletal actin has been discussed (see Figure 8). Work in Mandel s laboratory (Mandel, 1992) has revealed that other cytoskeletal proteins are also substrates for endogenous ADP-ribosyl transferase, including components of the microfilaments (tubulin, intermediate filaments, and the neurofilament proteins L, M, and H). 

Yamashita and co-workers reported that nicotinamide exhibit attaching repellent activity against the blue mussel (Mytilus edulis) [119]. Nicotinamide (34) is a product of NAD+ cleavage by mono (ADP-ribosyl) transferase, and it serves as an effective inhibitor of the enzyme activity... 

A number of pathogenic bacteria produce bacterial toxins that are ADP-ribosyl transferases (NAD+-glycohydrolases). These enzymes hydrolyze the N-glycosidic bond of NAD+ and transfer the ADP-ribose portion to a specific amino acid residue on a protein in the affected human cell. Cholera A-B toxin, a pertussis toxin, and a diptheria toxin are all ADP-ribo-syl transferases. 

Mono- and poly-ADP-ribosylation. Mono-ADP-ribosylation and poly(ADP-ribose) modification catalyzed by ADP-ribosyl transferase and poly(ribose) synthetase respectively, append mono- and poly ADP-ribose (ADPR) moieties (Hayaishi and Ueda, 1977). In poly ADPR, the polymeric chain consists of woADP-ribose, 2 -(5"-phosphoribosyl)-5 -AMP... 

Inactivation of Rho with Clostridium botulinum C3 ADP-ribosyl-transferase (C3 exoenzyme, which specifically ADP-ribosylates and inactivates Rho) inhibits neutrophil chemotaxis to N-formyl peptides [369, 443] without inhibiting the initiation of actin polymerization [94]. Microscopic examination of these cells reveals that they are unaffected in their abilities to polarize and extend pseudopodia, rather C3 exoenzyme inhibition of migration is associated with inhibition of rear release. 

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