ADP-ribosyltransferases

ADP-ribosyltransferases are enzymes of the cytosol, plasma membrane, and nuclear envelope that catalyze the transfer of ADP-ribose onto arginine. 

In the absence of an acceptor protein, ADP-ribosyltransferase catalyzes the hydrolysis of NAD+ to release nicotinamide and free ADP-ribose. The carboxy terminal region of the enzyme has NAD glycohydrolase activity, but does not catalyze the transfer of ADP-ribose onto target proteins. 

The ribosomal elongation Factor II is the acceptor protein for the ADP-ribosyltransferase activity of diphtheria toxin and P. aeruginosa exotoxin A, as well as a mammalian cytosolic ADP-ribosyltransferase. ADP-ribosylation results in loss of activity. The uncontrolled action of the bacterial toxins causes the cessation of protein synthesis and hence cell death. The more regulated action of the endogenous ADP-ribosyltransferase is part of the normal regulation of protein synthesis. 

A variety of guanine nucleotide binding proteins (G-proteins) involved with the regulation of adenylate cyclase activity and transducin in the retina (Section 2.3.1) are substrates for ADP-ribosylation. Cholera toxin and E. coli enterotoxin LT ADP-ribosylate, and hence activate, the stimulatory G-protein of adenylate cyclase, whereas pertussis toxin ADP-ribosylates, and inactivates the inhibitory G-protein of adenylate cyclase. The result of ADP-ribosylation by either mechanism is increased adenylate cyclase activity, and an increase in intracellular cAMP and the opening of membrane calcium channels. Again, there are endogenous ADP-ribosyltransferases that modify the same G-proteins, but in a controlled manner (Moss et al., 1997, 1999). 

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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.]... 

Some bacterial toxins have their effects on humans by interfering with the activity of the G-protein, that is G-proteins are involved in the action of some toxins, e.g. cholera toxin and pertussis toxin. Cholera toxin is a protein (mol. mass 87 kDa) consisting of A and B subunits, produced by the bacterium Vibrio cholerae. Subunit B binds to the plasma membrane of an intestinal ceU and then the A subimit enters the ceU. This subunit possesses ADP-ribosyltransferase activity, an activity which transfers the ADP-ribose from NAD to the a-subunit of G-protein,... 

Ahuja, N., Schwer, B., Carobbio, S., Waltregny D., North, B.J., Castronovo, V., Maechler, P. and Verdin, F. (2007) Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase. The Journal of Biological Chemistry, 282, 33583-33592. 

Liszt, G., Ford, E., Kurtev, M. and Guarente, L. (2005) Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. The Journal of Biological Chemistry, 280, 21313-21320. 

This enzyme [EC 4.6.1.1], also known as adenylyl cyclase and 3, 5 -cyclic AMP synthetase, catalyzes the conversion of ATP to 3, 5 -cyclic AMP and pyrophosphate. The enzyme requires pyruvate as a cofactor and will also utilize dATP as a substrate (thereby producing 3, 5 -cyclic dAMP). In the presence of NAD(P) -arginine ADP-ribosyltransferase, this enzyme is activated by covalent modification. 

Covalent modification of a protein by the hnkage of an ADP-ribosyl moiety to the protein. The resulting product typically exhibits altered kinetic and/or regulatory properties. ADP-ribosyltransferases catalyze the trans-... 

An ADP-ribosyltransferase that permanently activates the Gs regulatory protein in the adenylate cyclase pathway. Because ADP-ribosylated Gs GTP complex cannot be converted to its metabolic inactive form, the adenylate cyclase remains in its activated state. The following are recent reviews on the molecular and physical properties of this ADP-ribosylating enzyme. 

This enzyme [EC 2.4.2.30] (also referred to as NAD+ ADP-ribosyltransferase, poly(ADP) polymerase, poly-(adenosine diphosphate ribose) polymerase, and ADP-ribosyltransferase (polymerizing)) catalyzes the reaction of NAD+ with [ADP-D-ribosyl] to produce nicotinamide and [ADP-D-ribosyl]( + i). The ADP-d-ribosyl group of NAD+ is transferred to an acceptor carboxyl group on a histone or on the enzyme itself, and further ADP-ribosyl groups are transferred to the 2 -position of the terminal adenosine moiety, building up a polymer with an average chain length of twenty to thirty units. 

Brune, B., and Lapetina, E. G. (1990). Properties of a novel nitric oxide-stimulated ADP-ribosyltransferase. Arch. Biochem. Biophys. 279, 286-290. 

Brune and Lapetina (1989) reported that NO could activate a platelet ADP-ribosyltransferase that resulted in the ribosylation of a 39 kDa protein. Subsequent work revealed that the protein was glyceraldehyde phosphate dehydrogenase (GAP-DH), and that ribosylation was associated with reduced GAP-DH activity (Dimmeler et al., 1992). In our collaboration with Molina et al., (1992), we have shown that GAP-DH activity is dramatically inhibited in C. parvum treated rats and that this action is associated with both a ribosylation and nitro-sylation of the enzyme. Such a marked inhibition of a glycolytic enzyme could explain some of the metabolic changes observed in the liver in sepsis. 

What is the origin of the tox gene, and why is it carried by a virus Cells do normally contain ADP-ribosyltransferases J The genes for such a protein may have become incorporated into a virus and, after a period of evolution, came to specify the toxic protein. 

Schuman EM, Meffert MK, Schulman H, Madison DV (1994) An ADP-ribosyltransferase as a potential target for nitric oxide action in hippocampal long-term potentiation. Proc Nad Acad Sci USA 91 11958-62... 

Tohda M, Tohda C, Oda H, Nomura Y. Possible involvement of botulinum ADP-ribosyltransferase sensitive low molecular G protein on 5-hydroxytryptamine (5-HT)-induced inositol phosphates formation in 5-HT2c cDNA transfected cells. Neurosci Lett 1995 190 33-36. 

Figure 8.2. Synthesis of NAD from nicotinamide, nicotinic acid, and qninolinic acid. Quinolinate phosphoribosyltransferase, EC 2.4.2.19 nicotinic acid phosphoribosyl-transferase, EC 2.4.2.11 nicotinamide phosphoribosyltransferase, EC 2.4.2.12 nicotinamide deamidase, EC 3.5.1.19 NAD glycohydrolase, EC 3.2.2.S NAD pyrophosphatase, EC 3.6.1.22 ADP-ribosyltransferases, EC 2.4.2.31 and EC 2.4.2.36 and poly(ADP-ribose) polymerase, EC 2.4.2.30. PRPP, phosphoribosyl pyrophosphate.

ADP-ribosyltransferase, which catalyzes ADP-ribosylation of proteins, releasing nicotinamide (Section 8.4.2). 

NAD is the source of ADP-ribose for the modification of proteins by mono-ADP-ribosylation, catalyzed by ADP-ribosyltransferases (Section 8.4.2), and poly(ADP-ribosylation), catalyzed by poly(ADP-ribose) polymerase (Section 8.4.3). It is also the precursor of two second messengers that act to increase the intracellular concentration of calcium, cADP-ribose, and nicotinic acid adenine dinucleotide phosphate (Section 8.4.4). 

Figure 8.6. Reactions of ADP-ribosyltransferase (EC 2.4.2.31) and poly(ADP-ribose) polymerase (EC 2.4.2.30).

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