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)

Ribosome-inactivating proteins (RIPs) are a group of proteins that inhibit protein synthesis in eucaryotic cells. While the biological effects have been well characterized, the underlying enzymatic mechanisms have not been elucidated until recently. Two different mechanisms have been identified. Plant and bacterial RIPs act as N-glycosidases. They cleave a single N-glycosidic bond between adenine and ribose at a specific nucleotide A-4324 of the 28S rRNA of the 60S ribosomal subunit. On the other hand, the fungal RIPs act as ribonucleases and cleave a single phosphodiester bond between G-4325 and A-4326 of the same rRNA, just one nucleotide away from the site of action of plant/bacterial RIPs. Other protein synthesis inhibitory proteins act by their ADP-ribosyltransferase activity which modify and thus inactivate elongation factor-2. Recently, some toxins have been shown to possess deoxyribonuclease activity which may also account for their toxicity.
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PMID:Minireview: enzymatic properties of ribosome-inactivating proteins (RIPs) and related toxins. 174 1

We have recently devised an activity-blot procedure permitting the detection, on the same nitrocellulose sheet, of the functional poly(ADP ribose) polymerase (PARP) activity as well as the immunostained active peptide(s) after renaturation of the transferred protein(s). Using this technique we have analyzed the PARP activity in higher and lower eukaryotes directly on crude extracts from cell cultures. This procedure has been extended also to in situ screening of bacterial colonies expressing the PARP enzymatic activity.
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PMID:Detection of poly(ADP ribose) polymerase in crude extracts by activity-blot. 175 Jun 71

We have reported the purification and characterization of arginine-specific ADP-ribosyltransferase from hen liver nuclei [Tanigawa, Y. et al. (1984) J. Biol. Chem. 259, 2022-2029] and the DNA-dependent mono(ADP-ribosyl)ation of p33, an acceptor protein in the nuclei [Mishima, K. et al. (1989) Eur. J. Biochem. 179, 267-273]. In the present study, we obtained evidence that among various tissues and cells from chicken, polymorphonuclear cells, so-called heterophils, possess both the ADP-ribosyltransferase and p33 at high levels. Percoll density gradient centrifugation of the postnuclear fraction of the heterophils revealed the co-localization of ADP-ribosyltransferase with p33 in the granule fraction. The enzyme and p33 were purified approximately 219- and 3.77-fold, respectively, from postnuclear pellet fraction to apparent homogeneity. The properties of heterophil ADP-ribosyltransferase and p33 were compared with those of the liver enzyme and p33. The molecular mass of the heterophil enzyme was estimated by SDS-polyacrylamide gel electrophoresis to be 27.5 kDa. The enzyme activity was stimulated by a sulfhydryl agent and inhibited by lysolecithin, NaCl, and inorganic phosphate. The mono(ADP-ribosyl)ation of p33 was markedly enhanced by polyanion, such as DNA, RNA, or poly(L-glutamate). SDS-polyacrylamide gel electrophoretic analysis after limited trypsin proteolysis of p33s, purified from chicken heterophils and liver, showed much the same pattern. Thus, it appears that ADP-ribosyltransferase and p33 present in heterophils are identical to those in the liver, respectively. p33 is considered to be an in situ substrate for ADP-ribosyltransferase, since it was specifically mono(ADP-ribosyl)ated in permeabilized heterophils.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Arginine-specific ADP-ribosyltransferase and its acceptor protein p33 in chicken polymorphonuclear cells: co-localization in the cell granules, partial characterization, and in situ mono(ADP-ribosyl)ation. 176 68

The monoclonal antibody termed 1B7 neutralizes pertussis toxin in vivo in cell culture systems and can also passively protect mice from a challenge with live Bordetella pertussis (9). It has been suggested that most other independently derived neutralizing monoclonal antibodies recognizing the S1 subunit apparently recognize the same epitope as 1B7, and that the S1 subunit contains only one immunodominant protective epitope (1). These antibodies have been termed Class A antibodies (8) and inhibit the ADP-ribosyltransferase but not the NAD glycohydrolase activity of the toxin (7). We are testing the hypothesis that immunization with inactivated preparations of pertussis toxin that lead to protection are associated with the production of Class A antibodies. If true, then identification of Class A antibodies in sera might provide a serological correlate of protection. If false, then development of assays designed to detect the important protective antibodies are necessary. Our initial results suggest that Class A antibodies are not the predominant neutralizing antibody in mice immunized with vaccines containing formalin-treated pertussis toxin.
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PMID:Evaluation of antibodies elicited by immunization with pertussis toxin. 177 8

Pretreatment of rho protein purified from pig brain cytosol with EDTA (3 mM) for 10 min at 30 degrees C inhibited its ADP-ribosylation by Clostridium botulinum C3 ADP-ribosyltransferase by more than 90%. The EDTA effect was not caused by alteration of C3. GDP or GDP beta S present during the pretreatment period completely prevented the decrease in ADP-ribosylation with half-maximal and maximal effects at 3 and 300 microM, respectively. GTP or GTP gamma S were less efficacious in preventing the decrease in ADP-ribosylation, but were more potent (half-maximal and maximal effects at 0.1 and 3 microM, respectively). [32P]ADP-ribose incorporated in pig brain rho by C3 was de-ADP-ribosylated by the enzyme in the presence of nicotinamide and at low pH. Concomitantly, [32P]NAD was formed. The pH optima for ADP-ribosylation and de-ADP-ribosylation were pH 7.5 and 5.5, respectively. De-ADP-ribosylation was most efficient with nicotinamide, less effective with 3-acetylpyridine and not observed with 3-aminopyridine, 4-aminopyridine, 4-acetylpyridine and isonicotinic acid. As observed for the ADP-ribosylation, the de-ADP-ribosylation by C3 was maximal with the GDP-bound form of rho and blocked after EDTA treatment.
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PMID:ADP-ribosylation and de-ADP-ribosylation of the rho protein by Clostridium botulinum exoenzyme C3. Regulation by EDTA, guanine nucleotides and pH. 182 95

Membrane-associated tumor necrosis factor (TNF) and soluble TNF were compared as to their lytic activities, and as to the kinetics of their expression by macrophages activated with LPS and/or IFN-gamma in the presence or absence of cycloheximide. EL 4 tumor cells, resistant and sensitive to lysis by recombinant TNF or membrane-associated TNF (paraformaldehyde (PF)-fixed activated macrophages) were used as targets. In the presence of cycloheximide the TNF-resistant S-EL4 cells were lysed by both TNFs. PF-fixed macrophages was cytolytic after 1 hr activation but not after 3 or more hours of activation. Their activity was totally inhibited by anti-TNF antibodies and was a composite of transmembrane (integral) TNF and soluble TNF conjugated to macrophage membrane TNF receptors. Treatment of the macrophages with glycine pH 3.0 buffer dissociated the conjugated TNF without affecting the integral membrane TNF. When macrophages were activated with LPS +/- IFN-gamma in the presence of cycloheximide or activated just with IFN-gamma their activity after fixation with paraformaldehyde was no longer detected. Nonfixed macrophages under these conditions still remained cytotoxic. Tumor cell susceptibility to membrane-associated TNF activity, in contrast to recombinant (soluble) TNF, was greatly reduced in the presence of nicotinamide, an inhibitor of ADP-ribosyltransferase, suggesting that the mechanisms of lysis by these TNFs may be different. The lytic activity of both TNFs was found to be receptor-dependent in that tumor cells, whose TNF binding sites were "down-regulated" by TPA, were rendered resistant to lysis by both membrane-associated and soluble TNFs.
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PMID:Cytolytic activities of activated macrophages versus paraformaldehyde-fixed macrophages; soluble versus membrane-associated TNF. 183 87

A cosmid library was prepared from a partial BamHI digest of total DNA from Bacillus sphaericus SSII-1. Two hundred fifty Escherichia coli clones were screened for toxicity against larvae of the mosquito Culex quinquefasciatus. One toxic clone, designated pKF2, was chosen for further study. Two toxic subclones, designated pXP33 and pXP34, obtained by ligating PstI-derived fragments of pKF2 into pUC18, contained the same 3.8-kb fragment, but in opposite orientations. Sequence analysis revealed the presence of an open reading frame corresponding to a 100-kDa protein and the 3' end of a further open reading frame having significant homology to open reading frames of transposons Tn501 and Tn21. The sequence of the SSII-1 toxin was compared with those of known toxins and was found to show regional homology to those of ADP-ribosyltransferase toxins. The distribution of the toxin gene among other B. sphaericus strains was examined.
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PMID:Cloning, sequencing, and expression of a gene encoding a 100-kilodalton mosquitocidal toxin from Bacillus sphaericus SSII-1. 184 May 81

Expression of the NAD+ ADP-ribosyltransferase gene is depressed during interferon-gamma-induced activation of murine macrophage P388D1 tumor cells [Taniguchi, T., Yamauchi, K., Yamamoto, T., Tokushima, K., Harada, N., Tanaka, H., Takahashi, S., Yamamoto, H. & Fujimoto, S. (1988) Eur. J. Biochem. 171, 571-575]. In order to study the role(s) of NAD+ ADP-ribosyltransferase in interferon-gamma-induced activation of P388D1 cells, we transfected an cloned synthetase gene into P388D1 cells and examined the effect of exogenous transferase gene expression on the induction of the Ia antigen, one of the major histocompatibility gene products, by interferon-gamma. The transferase activity of the transfected cells was twice that of control cells, and Southern blot analysis revealed that characteristic restriction sizes of cDNA were detected in the clones. RNA blot analysis using a cDNA for the transferase as a probe showed that the level of mRNA for the transferase in transfected cells was higher than that in control cells, and mRNA for the exogenous transferase was still detectable 2 days after the transfected cells were treated with interferon-gamma. This indicates that the exogenous transferase gene was expressed in transfected cells. RNA blot analysis with a cDNA for the Ia antigen and flow-cytometric analysis showed that the Ia antigen was induced much less in the transfected cells by interferon-gamma, in terms of the mRNA and the Ia antigen. The results suggest that down-regulation of the transferase is required for the induction of the Ia antigen in P388D1 cells by interferon-gamma.
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PMID:Requirement of down-regulation of NAD+ ADP-ribosyltransferase for the interferon-gamma-induced activation process of murine macrophage tumor cells. 184 88

Two enzymatic activities of the nuclear enzyme poly(ADP-ribose) polymerase or transferase (ADPRT, EC 2.4.2.30), a DNA-associating abundant nuclear protein with multiple molecular activities, have been determined in HL60 cells prior to and after their exposure to 1 microM retinoic acid, which results in the induction of differentiation to mature granulocytes in 4-5 days. The cellular concentration of immunoreactive ADPRT protein molecules in differentiated granulocytes remained unchanged compared to that in HL60 cells prior to retinoic acid addition (3.17 +/- 1.05 ng/10(5) cells), as did the apparent activity of poly(ADP-ribose) glycohydrolase of nuclei. On the other hand, the poly(ADP-ribose) synthesizing capacity of permeabilized cells or isolated nuclei decreased precipitously upon retinoic acid-induced differentiation, whereas the NAD glycohydrolase activity of nuclei significantly increased. The nuclear NAD glycohydrolase activity was identified as an ADPRT-catalyzed enzymatic activity by its unreactivity toward ethenoadenine NAD as a substrate added to nuclei or to purified ADPRT. During the decrease in in vitro poly(ADP-ribose) polymerase activity of nuclei following retinoic acid treatment, the quantity of endogenously poly(ADP-ribosylated) ADPRT significantly increased, as determined by chromatographic isolation of this modified protein by the boronate affinity technique, followed by gel electrophoresis and immunotransblot. When homogenous isolated ADPRT was first ADP-ribosylated in vitro, it lost its capacity to catalyze further polymer synthesis, whereas the NAD glycohydrolase function of the automodified enzyme was greatly augmented. Since results of in vivo and in vitro experiments coincide, it appears that in retinoic acid-induced differentiated cells (granulocytes) the autopoly(ADP-ribosylated) ADPRT performs a predominantly, if not exclusively, NAD glycohydrolase function.
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PMID:Cellular regulation of ADP-ribosylation of proteins. IV. Conversion of poly(ADP-ribose) polymerase activity to NAD-glycohydrolase during retinoic acid-induced differentiation of HL60 cells. 184 25

Trypsin digestion of pertussis toxin (PT) preferentially cleaved the S1 subunit at Arg-218 without detectable degradation of the B oligomer. The fragment produced, termed the tryptic S1 fragment, appears to remain associated with the B oligomer. Chymotrypsin digestion of PT also preferentially cleaved the S1 subunit without detectable degradation of the B oligomer. The chymotryptic S1 fragment possessed a slightly lower apparent molecular weight than the tryptic S1 fragment and was more accessible to the respective protease. Trypsin- and chymotrypsin-treated PT and PT required the presence of dithiothreitol and ATP for optimal enzymatic activity. Trypsin-treated PT showed approximately a 2-4-fold higher level of expression of ADP-ribosyltransferase and NAD-glycohydrolase activities than PT. Chymotrypsin-treated PT also exhibited approximately a 2-fold greater level of ADP-ribosyltransferase activity than PT. The observed increase in activity of protease-treated PT was due primarily to a shorter time for activation in PT mediated ADP-ribosylation of transducin. In addition, trypsin-digested PT possessed the same cytotoxic potential for Chinese hamster ovary cell clustering as PT. One possible role for the generation of a proteolytic fragment of the S1 subunit of PT would be to produce a catalytic fragment with increased efficiency for ADP-ribosylation of G proteins in vivo.
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PMID:Protease treatment of pertussis toxin identifies the preferential cleavage of the S1 subunit. 185 Jul 38


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