Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cloned library of DNA complementary to the mRNA of adult Schistosoma japonicum has been prepared and expressed as fusion proteins with Escherichia coli beta-galactosidase. Colonies expressing the S. japonicum cDNA clones were screened both with antibodies from individuals with a history of schistosomiasis and with antibodies obtained from a rabbit immunized with whole adult worms. In both cases colonies were detected which bound antibody, although the frequency of antigen-positive clones was much higher with the rabbit antiserum than with human sera. In both cases the proportion of colonies reacting with antibodies was markedly lower than that published for equivalent screens of Plasmodium falciparum cDNA with sera from individuals with a history of falciparum malaria. Several major S. japonicum antigens were identified by the affinity purification of antibodies using immobilised fusion proteins produced during lytic growth of the recombinant bacteriophage.
Mol Biochem Parasitol 1986 Mar
PMID:Expression of Schistosoma japonicum antigens in Escherichia coli. 351 79

The involvement in the immunity to schistosomiasis of an aminopeptidase activity of schistosomula, 20-day-old and adult worms of Schistosoma mansoni has been studied. This activity, hydrolysing leucine-p-nitroanilide and alanine-p-nitroanilide at pH 7.4 was immunoprecipitated by various infected rat and human sera. These antigenic enzymes were expressed at day 28 after infection in the rat and seemed to be specific for the Schistosoma species. Several aminopeptidase activities were found after analysis by isoelectric focusing of the adult extract but only the pI 8.3 peak was antigenic. Three antigenic peaks were demonstrated after AcA 34 Ultrogel filtration. The biological relevance of these antigenic enzymes in schistosomiasis is discussed.
Mol Biochem Parasitol 1982 Nov
PMID:Antigenic properties of Schistosoma mansoni aminopeptidases: evolution during the development in mammalian hosts. 717 66

Surface antigens of Schistosoma mansoni schistosomula were isolated using antibodies produced in rat and human schistosomiasis. Three immunoreactive surface proteins of 40 000, 37 000 and 32 000 daltons were identified by SDS-PAGE analysis of immune complexes formed by incubation of a detergent extract of surface labelled schistosomula with infected rat sera. Surface antigens of similar molecular weight were also isolated when using sera of patients with schistosomiasis. Binding of schistosomula surface antigens to specific antibodies was substantially inhibited by components released by adult worms. The results suggest that these schistosomula surface antigens could be involved in the immune response against challenge infection but their protective role in immunity still remains to be determined.
Mol Biochem Parasitol 1981 Aug
PMID:Isolation and characterization of surface antigens from Schistosoma mansoni schistosomula. 727 81

Glutathione S-transferase (GST), an essential detoxification enzyme in parasitic helminths, is a major vaccine target and an attractive drug target against schistosomiasis and other helminthic diseases. Crystal structures of the 26 kDa GST from the helminth Schistosoma japonica (SjGST) have been determined for the unligated enzyme (resolution = 2.4 A, R-factor = 19.7%) and for the enzyme bound to the leading antischistosomal drug praziquantel (resolution = 2.6 A, R-factor = 21.2%). The protein, recombinantly expressed using the Pharamacia PGEX-3X vector for production of GST fusion proteins, contains all 218 residues of SjGST and an additional 13 residues at the C terminus. The structure of unligated SjGST shows that the glutathione binding site pre-exists unchanged in the ligand-free enzyme and is conserved between parasitic and the mammalian class mu enzymes. At therapeutic concentrations the leading antischistosomal drug praziquantel (PZQ) binds one drug per enzyme homodimer in the dimer interface groove adjoining the two catalytic sites. This establishes a protein target for PZQ, identifies the GST non-substrate ligand transport site, and implicates PZQ in steric inhibition of SjGST catalytic and transport for large ligands. Thus, increased expression or mutagenesis of SjGST by the parasite may confer resistance to PZQ. Differences in the xenobiotic binding region between parasitic and mammalian GSTs reveal a distinct substrate repertoire for SjGST and, together with the newly identified PZQ binding site, provide the basis for design of novel antischistosomal drugs. Due to the widespread use expression systems based on SjGST fusions, the atomic structure of SjGST should also provide an important tool for phasing fusion protein structures by molecular replacement.
J Mol Biol 1995 Feb 10
PMID:Crystal structures of a schistosomal drug and vaccine target: glutathione S-transferase from Schistosoma japonica and its complex with the leading antischistosomal drug praziquantel. 785 99

Immunological crossreactivity among nematodes has hampered development of specific serodiagnostic assays for lymphatic filariasis. In the present study, we report the molecular cloning and characterization of two filaria-specific recombinant clones (BmM5 and BmM14) with immunodiagnostic potential. BmM5 is a 505-bp cDNA which codes for a protein of 130 residues that ends with an endoplasmic reticulum targeting sequence. BmM14 is closely related to a recently reported clone (SXP-1), and it has 62% homology (deduced amino acid sequence) with a previously described Onchocerca volvulus clone, lambda RAL-2. Glutathione S-transferase fusion proteins of BmM5 and BmM14 were tested in various ELISA formats. The best results were obtained by measuring IgG4 antibodies to the fusion proteins. ELISA studies showed that approximately 90% of 111 sera from Indian and Egyptian patients with brugian and bancroftian filariasis were reactive with both antigens. Nonendemic sera as well as sera from patients with schistosomiasis or intestinal helminths were uniformly nonreactive. Assays based on BmM5 and BmM14 may be useful for large scale screening as an alternative to microfilaria or filarial antigen detection as a means of obtaining a rough index of filariasis endemicity in previously unstudied areas.
Mol Biochem Parasitol 1994 Apr
PMID:Molecular cloning of Brugia malayi antigens for diagnosis of lymphatic filariasis. 793 4

Among the synthetic peptides derived from the 28-kDa Schistosoma mansoni glutathione S-transferase (Sm28GST), immunization with the C-terminal peptide comprising amino acid residues 190-211 induced a reduction in splenomegaly, in the number of hepatic eggs and in hepatic fibrosis in mice infected by Schistosoma mansoni. The absence of antibodies specific for the Sm28GST or for the 190-211 peptide observed in our conditions of immunization with this peptide argued in favour of the involvement of cellular-dependent mechanisms in the reduction in hepatic pathology. This was confirmed by the passive transfer of 190-211 peptide-specific T-cell enriched spleen cells which reproduced the protective effect conferred by immunization with the 190-211 peptide. These 190-211 peptide-specific cells produced little IL4 and high levels of IFN-gamma, a potent inhibitor of collagen synthesis. Furthermore, the use of a lipopeptidic form of the 190-211 peptide significantly improved the reduction in hepatic pathology obtained with the uncoupled peptide and induced a durable protective response. These results provide encouraging information for the possible use of synthetic peptides in the immunoprophylaxis of Schistosomiasis.
Mol Immunol 1994 Nov
PMID:Evaluation of the effect of Sm28GST-derived peptides in murine hepatosplenic schistosomiasis: interest of the lipopeptidic form of the C-terminal peptide. 796 86

The activities of catalase (H2O2-oxidoreductase EC 1.11.1.6)- and glutathione reductase (EC 1.6.4.2) as two important scavenger enzymes, were measured in tissue homogenates of Biomphalaria alexandrina and Bulinus truncatus, the snail vectors of Schistosomiasis. A parallel study was done on Lymnea truncatula snails which are not susceptible to Schistosoma infection. The apparent Michaelis constant (Km) for both anzymes were determined in tissue homogenates of the three studied species. The results obtained showed that both susceptible species have higher affinity to hydrogen peroxide (H2O2) and oxidized glutathione (GSSG) than the non-susceptible one.
Cell Mol Biol (Noisy-le-grand) 1993 Jun
PMID:Kinetic potentials of certain scavenger enzymes in fresh water snails susceptible and non-susceptible to Schistosoma infection. 832 84

"Sucupira" oil and the lactone eremanthine, extracted from Pterodon pubescens and Eremanthus elaeagnus, respectively, are known for their cercaricidal action in experimental animals. Because of their biological effect, they have the potential to be used for the prophylaxis of schistosomiasis caused by Schistosoma mansoni. To test the clastogenicity of these agents, "sucupira" oil, either pure or diluted in corn oil, was tested in vivo on Wistar rat bone marrow cells following dermal application. Metaphase analysis showed that the compound did not induce a significant increase in the frequencies of chromosomal aberrations. When eremanthine was tested on BALB/c mice following gavage at doses of 100, 200, and 300 mg/kg bw, it did not induce structural or numerical chromosomal aberrations. In the in vitro treatment of human lymphocyte cultures, eremanthine also did not cause any increase in chromosomal aberrations or sister chromatid exchanges at the following concentrations in culture medium: 1.25, 2.50, and 5.00 micrograms/ml. From these results, under our experimental conditions, neither "sucupira" oil nor eremanthine showed clastogenic effects on mammalian cells in vivo or in vitro.
Environ Mol Mutagen 1995
PMID:Genotoxicity of the natural cercaricides "sucupira" oil and eremanthine in mammalian cells in vitro and in vivo. 857 23

An important pathological outcome of schistosomiasis is hepatic fibrosis, with a significant deposit of collagens and proteoglycans. In this study, hepatic and granuloma-associated glycosaminoglycans (GAGs) were analyzed both quantitatively and qualitatively at the acute stage of murine infection with Schistosoma mansoni. The effects of IFN gamma, which has been successfully used for reducing collagen deposition in the liver during schistosomiasis, were also analyzed in granulomas and the surrounding liver parenchyma. Acute schistosomiasis resulted in a 4.4-fold increase in total hepatic GAG content, from which granulomatous GAGs--mainly chondroitin sulfates A/C and B--represented only one sixth of total GAGs amount. Therefore, the increase was found predominantly in the parenchyma. In this compartment, qualitative changes were also induced with a marked increase in the proportion of chondroitin sulfates A/C balanced by a decrease in the proportion of heparan sulfate and dermatan sulfate. IFN gamma reduced parenchymal GAG content by 47%. Qualitatively, the cytokine increased the proportion of heparan sulfate and reduced the quantity of chondroitin sulfates A/C by half in this compartment. By contrast, IFN gamma had neither quantitative nor qualitative effect on fibroinflammatory granulomas. In these structures, the absence of heparan sulfate--which is suspected to mediate IFN gamma activity--might explain these observations.
Cell Mol Biol (Noisy-le-grand) 1996 Mar
PMID:Distribution of hepatic glycosaminoglycans during acute schistosomiasis: modulation by IFN gamma treatment. 869 53

Schistosomiasis is a parasitic disease initiated by the deposition of eggs in host tissues by the blood fluke Schistosoma. A gene encoding a low-molecular weight GTP-binding protein (LMWGP) was cloned from Schistosoma mansoni using a polymerase chain reaction (PCR)-based strategy. The gene was termed smrab (Schistosoma mansoni rab-related protein). Northern blot analysis hybridizes smrab cDNA with a 1.5-kb band of mRNA; this mRNA is abundantly expressed in male schistosomes, while only slightly in females. The deduced amino acid sequence of smrab shares ca. 70% homology with that of several rab-related LMWGPs. Smrab terminates in a CCXXX motif, which is one of several signals for post-translational isoprenoid modification by geranylgeranyl protein transferase (GGPT) type II. A GGPT assay with in vitro translation product confirms that smrab is geranylgeranylated. Recombinant expression of smrab in the pET3a expression vector yields insoluble protein which migrates as a 23-kDa band on SDS-PAGE. N-terminal sequence information of the recombinant protein matches the predicted amino acid sequence of smrab. GTP-binding analysis indicates that the recombinant protein binds GTP. Therefore, smrab meets the criteria recently established for acceptance into the ras superfamily of GTP-binding proteins (Kahn, R.A., Der, C.J. and Bokoch, G.M. (1992) The ras superfamily of GTP-binding proteins: guidelines on nomenclature. FASEB J. 6, 2512-2513, Ref. [21]).
Mol Biochem Parasitol 1996 Apr
PMID:A rab-related GTP-binding protein in Schistosoma mansoni. 878 69


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