Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.4.2.30 (PARP)
13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An ADP-ribosyltransferase from turkey erythrocytes, which catalyzes the mono(ADP-ribosylation) of guanidino compounds such as arginine and of many purified and crude cellular proteins, appears to exist both in high-activity, histone-independent and low-activity, histone-dependent forms. At low salt concentrations, the activity of the transferase with agmatine as acceptor was less than 10% that observed in the presence of 200 mM NaCl. In the absence of salts, ADP-ribosylation of agmatine was stimulated greater than 10-fold by histones, and activity approached that observed with high salt concentration; under these conditions, the histones did not serve as ADP-ribose acceptors themselves. Histone also activated the highly purified ADP-ribosyltransferase from human erythrocytes. Enzyme activity was increased in the presence of salt and was then relatively independent of histones. DNA was not required for the stimulation of ADP-ribosylation by histone; incubation of the transferase and histone with DNase did not significantly decrease enzymatic activity. Additional DNA in the assay decreased the effect of histone. The erythrocyte ADP-ribosyltransferase from diverse species thus appears to exist in two forms: one is dependent on histones for activity and one which, in the presence of salt, has high intrinsic activity and is independent of histone. The fact that the active forms of the transferase generated in the presence of salt or histone have similar catalytic activity suggests that these forms of transferase may be identical. It would appear that the enzymatic activity of transferase from different species may be controlled by histones.
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PMID:Histone-dependent and histone-independent forms of an ADP-ribosyltransferase from human and turkey erythrocytes. 627 74

[adenine-U-14C]ADP-ribose-agmatine and [adenine-U-14C ))ADP-ribose-histone were synthesized by an NAD:arginine ADP-ribosyltransferase from [14C]NAD and agmatine and histone, respectively. The pseudo-first order rate constants for breakdown of the two components either in 0.4 N NaOH or in 0.4 M neutral hydroxylamine were identical. Hydroxylamine treatment of [14C]ADP-ribose-agmatine or [32P]ADP-ribose-histone yielded a single radioactive product which was separated by high pressure liquid chromatography and identified as ADP-ribose-hydroxamate by the formation of a ferric chloride complex. Hydrolysis of ADP-ribose-hydroxamate with snake venom phosphodiesterase resulted in the formation of 5'-AMP, consistent with the presence of a pyrophosphate bond. Incubation of ADP-ribose-[14C]agmatine, synthesized by the ADP-ribosyltransferase from NAD and [14C]agmatine, with 0.4 M neutral hydroxylamine resulted in the release of [14C]agmatine rather than phosphoribosyl[14C]agmatine. In addition, neither NAD nor ADP-ribose reacts with hydroxylamine; i.e. there was no evidence of nucleophilic attack by hydroxylamine at the pyrophosphate bond. The ADP-ribosyl-protein linkage formed by the NAD:arginine ADP-ribosyltransferase is considerably more stable to hydroxylamine than is the ADP-ribose-glutamate bond. The presence of ADP-ribose-arginine and ADP-ribose-glutamate synthesized by the ADP-ribosyltransferase and poly(ADP-ribose) synthetase, respectively, may be the chemical basis for the "hydroxylamine-stable" and "hydroxylamine-labile" bonds described by Hilz (Hilz, H. (1981) Hoppe-Seyler's Z. Physiol. Chem. 362, 1415-1425).
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PMID:Amino acid-specific ADP-ribosylation. 630 41

Pertussis toxin (islet-activating protein) activates adenylate cyclase in susceptible cells by ADP-ribosylating an inhibitory component of the cyclase system. This toxin, assayed in a cell-free system in the presence of high concentrations of thiol, catalyzed the hydrolysis of NAD to ADP-ribose and nicotinamide. This NAD glycohydrolase activity co-chromatographed on Sephacryl G-200 in 6.5 M urea, pH 3.2, 0.1 M glycine with the ADP-ribosyltransferase activity of the toxin, as monitored by the transfer of [32P]ADP-ribose from [32P]NAD to a 41,000-Da protein in NG108-15 neuroblastoma X glioma hybrid cells. In the absence of thiol, the native holotoxin was enzymatically inactive. Following addition of 250 mM dithiothreitol to the assay, maximal enzymatic activity was evident after a delay of approximately 1 h; with 20 mM thiol, the delay was longer. The Km for NAD with the fully activated enzyme was 25 microM; the Km did not appear to vary with the extent of activation. Thiol was necessary in a cell-free system to demonstrate NAD glycohydrolase activity. When extensively washed membranes were used as a source of 41,000-Da substrate, thiol was necessary to observe ADP-ribosylation in some cases (human erythrocytes) and significantly stimulated activity in others (NG108-15 cells). In contrast to the bacterial toxins choleragen and Escherichia coli heat-labile enterotoxin that ADP-ribosylate stimulatory components of the cyclase system, pertussis toxin did not transfer ADP-ribose to low molecular weight guanidino compounds, such as arginine or agmatine.
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PMID:Activation by thiol of the latent NAD glycohydrolase and ADP-ribosyltransferase activities of Bordetella pertussis toxin (islet-activating protein). 631 27

Chromatin-bound ADP-ribosyltransferase from adult hen liver nuclei was purified to a homogeneous state through salt extraction, gel filtration, hydroxyapatite, phenyl-Sepharose, Cm-cellulose, and DNA-Sepharose. The ADP-ribosyltransferase has a pH optimum at 9.0 and does not require DNA for reaction. The purified enzyme has a molecular weight of 27,500 +/- 500. Agmatine sulfate, arginine methyl ester, histones, and casein proved to be effective acceptors for the ADP-ribose molecule. Among histones, H3 was most active, followed by H2a, H4, and H2b, in that order, the lowest activity seen with H1. With all the acceptors tested, the rate of nicotinamide release was in excess of the ADP-ribosylation. However, changes in the ratio of nicotinamide release to ADP-ribosylation seemed to depend on concentrations of the acceptor used. ADP-ribose-whole histones X adducts formed by ADP-ribosyltransferase served as initiators for poly(ADP-ribose) synthesis when these adducts were incubated in the presence of NAD, DNA, Mg2+, and the purified poly(ADP-ribose) synthetase, in which poly(ADP-ribose) formation can occur.
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PMID:ADP-ribosyltransferase from hen liver nuclei. Purification and characterization. 631 19

In the presence of NAD+, renal brush-border membranes are mono-ADP-ribosylated by an endogenous ADP-ribosyltransferase. The reaction is inhibited by arginine methyl ester and is markedly stimulated by EDTA. Stimulation by EDTA is likely due, at least in part, to EDTA preventing the destruction of intact NAD+ by other enzymes in the brush-border membrane.
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PMID:Mechanism of stimulation of ADP-ribosyltransferase in the renal brush-border membrane by EDTA. 632 Aug 80

Two NAD: arginine ADP-ribosyltransferases (transferase "A" and "B") were identified in turkey erythrocytes and purified to homogeneity. Both transferases in the presence of NAD catalyzed the ADP-ribosylation of arginine, other low molecular weight guanidino compounds and proteins. ADP-ribosyltransferase A was activated by chaotropic salt or histone. Activation was associated with the disaggregation of an inactive, rapidly sedimenting, high molecular weight species to a protomeric form of approximately 28,000 daltons; this protomer in equilibrium aggregate transition was rapidly reversible. In the presence of salt, the Km's for NAD and arginine methyl ester were 15 microM and 1.3 mM, respectively; the turnover number for the purified enzyme was approximately 9,900 mol X min-1 X mol enzyme-1. ADP-ribosyltransferase B exhibited a substrate specificity clearly distinct from that of transferase A. Transferase B had a Mr of 32,000, slightly larger than that of the transferase A protomer. The activity of transferase B was unaffected by histone and inhibited by chaotropic salts; its Km's for NAD and arginine methyl ester of 36 microM and 3 mM, respectively, were similar to those obtained with transferase A. These studies are consistent with the presence of two different NAD: arginine ADP-ribosyltransferases in turkey erythrocytes exhibiting distinct kinetic, regulatory, and physical properties.
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PMID:Characterization of NAD: arginine ADP-ribosyltransferases in animal tissues. 641 12

The activity of an NAD:arginine ADP-ribosyltransferase was stimulated 4-6-fold by lysolecithin; lysolecithins containing long-chain fatty acids such as stearoyl (C18) and palmitoyl (C16) were more effective than those with shorter chains: C14 greater than C12 greater than C10 congruent to C8. The analogue lacking a fatty acid at C-1, alpha-glycerophosphocholine, was inactive as were choline, lysophosphatidic acid, lysophosphatidylserine, lysophosphatidylglycerol, lysophosphatidylethanolamine, lecithin, phosphatidic acid, phosphatidylserine, and phosphatidylethanolamine. Activation of the transferase was, however, also observed with certain nonionic (e.g., Triton X-100) and zwitterionic [3-[ ( cholamidopropyl ) dimethylammonio ]-1-propanesulfonate] detergents. The transferase was shown previously to be stimulated by chaotropic salts or histones; in the presence of maximally effective concentrations of lysolecithin, salt, and histone, the activity was similar to that observed in the presence of histone or salt alone. Maximal activation by lysolecithin and detergents was less than that observed with either salt or histone. It appears that activation by lysolecithin shows significant differences from that observed previously with histones or salt and can be mimicked by certain nonionic and zwitterionic detergents.
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PMID:Activation of an erythrocyte NAD:arginine ADP-ribosyltransferase by lysolecithin and nonionic and zwitterionic detergents. 642 4

An ADP-ribosyltransferase from turkey erythrocytes which utilizes proteins and low molecular weight guanidino compounds such as arginine and agmatine as ADP-ribose acceptors was stimulated by histones. The effect was specific in that choleragen, a bacterial mono(ADP-ribosyl)transferase that increased adenylate cyclase activity in animal cells, was not activated by histones. With the erythrocyte enzyme, histones decreased the apparent Km values for arginine methyl ester and agmatine and increased the stability of the transferase to thermal denaturation. Activation of the transferase by histones was rapid, with a minimal delay observed upon addition of histones to a histone-free assay. Activation by histones was reversed upon dilution of a sample containing histones into an assay mix free of histone. In the absence of histone, the transferase existed as a rapidly sedimenting species; in the presence of histone, the transferase sedimented as a protomer.
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PMID:Activation of an NAD:arginine ADP-ribosyltransferase by histone. 679 12

Cholera toxin catalyzed the ADP-ribosylation of a single plasma membrane protein (Mr 55 000) of both RL-PR-C rat hepatocytes and purified rat liver plasma membranes. Labeling of this protein from nicotinamide [2,8-3H]adenine dinucleotide was competitively inhibited by free arginine, but by no other amino acid tested, including lysine. The same protein was ADP-ribosylated from NAD+ endogenously, i.e., in the absence of toxin. This process was, however, not competitively inhibited by added arginine nor by any other amino acid tested lysine. Free ADP-ribose, even in 50-fold molar excess over the nicotinamide [2,8-3H]adenine dinucleotide substrate, did not reduce (by isotope dilution) the endogenous or cholera toxin-catalyzed labeling of the 55 000 dalton membrane protein. It is likely, therefore, that hepatocyte plasma membranes contain an ADP-ribosyltransferase, with a mechanism similar to that of the A subunit of cholera toxin, in that both transfer ADP-ribose to the same membrane protein and in that neither apparently produce free ADP-ribose as an intermediate. It is also clear that the acceptor residue in the 55 000 dalton protein is different for each process. Cholera toxin-catalyzed and endogenous transfer of ADP-ribose to the hepatocyte plasma membrane protein, in contrast to a pigeon erythrocyte system, required no cytosolic factors. The results indicate that ADP-ribosylation in cloned differentiated rat hepatocytes differs from that in pigeon erythrocytes in that the acceptor protein is larger (55 000 compared to 42 000 daltons), cytosolic factors are not required and transfer of ADP-ribose to the acceptor protein occurs endogenously.
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PMID:Endogenous and cholera toxin-catalyzed ADP-ribosylation of a plasma membrane protein by RL-PR-C cloned rat hepatocytes. 722 28

Arginine-specific ADP-ribosyltransferase activity was detected in chicken spleen membrane fraction and the activity was extracted by phosphatidylinositol-specific phospholipase C but not by 1 M NaCl or 1% Triton X-100. The transferase activity extracted from the spleen membrane was thiol-independent and was not inhibited by 200 mM NaCl. Zymographic analysis of the transferase, under non-reducing conditions, showed two forms of active bands corresponding to a molecular mass of 46 and 42 kDa. Thus, the presence of this novel arginine-specific ADP-ribosyltransferase, anchored to the membrane through glycosylphosphatidylinositol and different from previously cloned chicken transferases, AT1 and AT2, is being given further attention.
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PMID:A newly identified GPI-anchored arginine-specific ADP-ribosyltransferase activity in chicken spleen. 757 41


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