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)

To determine the location of the non-substrate-ligand-binding region in mammalian glutathione S-transferases, fluorescence-resonance energy transfer was used to calculate distances between tryptophan residues and protein-bound 8-anilinonaphthalene 1-sulphonate (an anionic ligand) in the human class-alpha glutathione S-transferase, and in a human Trp28-->Phe mutant class-pi glutathione S-transferase. Distance values of 2.21 nm and 1.82 nm were calculated for the class-alpha and class-pi enzymes, respectively. Since glutathione S-transferases bind one non-substrate ligand/protein dimer, the ligand-binding region, according to the calculated distances, is found to be located in the dimer interface near the twofold axis. This region is the same as that in which the parasitic helminth Schistosoma japonicum glutathione S-transferase binds praziquantel, a non-substrate drug used to treat schistosomiasis [McTigue, M. A., Williams, D. R. & Tainer, J. A. (1995) J. Mol. Biol. 246, 21-27]. Since the overall folding topology is conserved and certain features at the dimer interface are similar throughout the superfamily, it is reasonable to expect that all cytosolic glutathione S-transferases bind non-substrate ligands in the amphipathic groove at the dimer interface.
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PMID:Determination of a binding site for a non-substrate ligand in mammalian cytosolic glutathione S-transferases by means of fluorescence-resonance energy transfer. 891 46

Antibodies affinity purified against tegumental components of schistosomula were used to screen a Schistosoma mansoni lambda gt11 adult worm cDNA expression library. One of the reactive clones was determined by sequence analysis to encode a protein homologous to cyclophilins of other species, in particular cyclophilin A. The 0.8-kb cDNA clone contained an open reading frame of 483 nucleotides which corresponds to a translation product of 161 amino acids with a deduced molecular size of 17.7 kDa. We have chosen to designate this clone as S. mansoni p17.7 (Smp17.7). The overexpressed and purified recombinant Smp17.7 (rSmp17.7) was demonstrated to possess peptidylprolyl cis-trans isomerase (PPIase) or rotamase activity typical of cyclophilins. Western blot analysis of Nonidet P-40 and a total soluble extract of adult schistosomes probed with affinity-purified antisera to rSmp17.7, demonstrated the presence of this protein in the parasite. Immunofluorescence studies using the purified antisera indicates a localization in various tissues including the tegument and the gut. As cyclophilin is able to interact with cyclosporin A (CsA), which has been shown to be antischistosomal in mice infected with S. mansoni, the characterization of this S. mansoni cyclophilin homologue may allow a better understanding of the schistosomicidal nature of cyclosporin A and lead to a novel strategy of therapy for schistosomiasis.
Mol Biochem Parasitol
PMID:Identification and characterization of Schistosoma mansoni p17.7, a cyclophilin. 891 96

The main complication of Schistosomiasis is the development of liver fibrosis as a result of periovular granuloma in portal tract. This study was undertaken to evaluate the role of the worms in the liver, using the unisexual murine schistosomiasis model. Hepatic fibrosis and histopathological lesions were sequentially followed for 65 weeks in mice experimentally infected with male Schistosoma mansoni. Morphological study revealed that, from the 25th week post-infection, a diffuse fibrosis affected the main branches of the portal vascular system following the host inflammatory reaction, associated with the proliferation of myofibroblasts in situ. Quantitative methods confirmed that an increase of fibrotic deposit occurred during chronic unisexual infection from 25 to 50 weeks post-infection, as compared to controls (35.06 +/- 3.55% versus 27.41 +/- 2.56%) suggesting that antigenic substances secreted by adult schistosomes, in the absence of any eggs, might initiate periportal and perisinusoidal fibrous reaction. The cytokine production and the evolution of inflammation towards fibrosis involves stellate cells and myofibroblasts stimulation. This fibrotic process consequently traduces a reparative phenomenon of the liver.
Cell Mol Biol (Noisy-le-grand) 1998 Jun
PMID:Liver fibrosis in unisexual murine Schistosomiasis: quantitative study and morphological changes in mice with chronic infection. 967 98

Alpha 3-fucosylation of protein or lipid substrates is an important component of the host/parasite interactions during schistosomiasis. In this process, alpha3-fucosyltransferases (alpha3-FucTs) are considered as key enzymes ensuring both parasite survival and adaptation in their (in)vertebrate hosts. In this paper, we report the molecular cloning of a putative alpha3-FucT from Schistosoma mansoni that we termed SmFucTA. The full-length SmFucTA encodes a typical transmembrane type II protein with a short cytoplasmic domain, a transmembrane segment and a long C-terminal catalytic domain. In this region, the GDP-fucose binding site is well conserved whereas the putative acceptor site displays sequence divergence compared to the corresponding region from vertebrate and invertebrate alpha3-FucTs. Southern blot analysis suggested that SmFucTA is present as several copies or has highly related counterparts in the S. mansoni genome. Northern blot revealed a single SmFucTA transcript at 2 kb in adult worms. Affinity purified antibodies directed against recombinant SmFucTA identified a 50 kDa native protein that localizes to the subtegumental and parenchymal regions of adult worms.
Mol Biochem Parasitol 2000 Apr 15
PMID:Molecular cloning of a putative alpha3-fucosyltransferase from Schistosoma mansoni. 1077 4

The glycolipids of Schistosoma mansoni adult worms, cercariae and eggs are recognised by schistosome infection serum and the monoclonal antibody M2D3H. The haemocyanin of the keyhole limpet, Megathura crenulata, is known to be immunoreactive to schistosomal infection sera and is, therefore, under investigation for the diagnosis of and vaccination against schistosomiasis. By dot-blot, inhibition-ELISA and inhibition-HPTLC immunostaining we have demonstrated that the M2D3H epitope is shared by both S. mansoni glycolipids and keyhole limpet haemocyanin (KLH). Analogously to the established epitopic importance of fucose to the immunorecognition of S. mansoni glycolipids, we have similarly defined the significance of the fucose residue(s) for the immunoreactivity between KLH and schistosomal infection serum and the monoclonal antibody M2D3H. Fucose was specifically removed from KLH by partial hydrolysis, monitored by ultrafiltration and carbohydrate component analysis. On removal of the fucose residue(s) the serological and immunological reactivity of KLH was greatly diminished, which implied that the fucose-containing M2D3H antigenic determinant was common to both S. mansoni glycolipids and KLH.
Mol Biochem Parasitol 2000 Oct
PMID:A fucose-containing epitope is shared by keyhole limpet haemocyanin and Schistosoma mansoni glycosphingolipids. 1107 Dec 79

Carnosine is a naturally occurring dipeptide (beta-alanyl-L-histidine) found in muscles, brain and other tissues. This study was designed to test the ability of carnosine to offset metabolic disturbances induced by Schistosoma mansoni parasitism. Results indicate that parasitic infection caused elevation of liver weight/body weight in S. mansoni-infected hamsters, induced lipid peroxidation and reduced glycogen levels. Moreover, adenylate energy charge (AEC) and ATP/ADP and ATP/AMP concentration ratios were markedly lower in infected hamsters. Administration of carnosine (10 mg/day) for 15 days concurrent with infection effectively reduced worm burden and egg count. Administration of carnosine 2 and 4 weeks post-exposure only partially ameliorated the S. mansoni effects on metabolism. Carnosine treatment also normalized most of the parameters measured, including glycogen repletion, the antioxidant status and AEC. These finding support the use of carnosine for possible intervention in schistosomiasis.
Comp Biochem Physiol B Biochem Mol Biol 2001 May
PMID:Effect of carnosine administration on metabolic parameters in bilharzia-infected hamsters. 1133 59

We tested the ability of carnosine to improve some liver disorders induced by Schistosoma mansoni parasite in hamsters (Mesocricetus auratus). Results indicate that parasitic infestation induced elevation in serum alkaline phosphatase, gamma-glutamyl transferase, aspartate aminotransferase and procollagen III peptide as a marker of liver fibrosis. Administration of carnosine (10 mg/day) for 15 days either concurrent with infection, 2 and 4 weeks post-infestation was effective in reducing differential worm burden. It was also effective in renormalizing blood glucose level depending on the time course. The most evident effect of carnosine was on serum procollagen III peptide level, which was lowered in infested groups treated with carnosine. Histopathological studies confirmed the potential use of carnosine for intervention in schistosomiasis.
Comp Biochem Physiol B Biochem Mol Biol 2002 Mar
PMID:Effects of carnosine on bilharzial infestation in hamsters: biochemical and histochemical studies. 1195 36

Biomphalaria glabrata is the main intermediate host of Schistosoma mansoni in America and one of the most intensely studied species of freshwater snails, yet very little is known about its population biology. Here, we used seven highly polymorphic microsatellite loci to analyse genetic diversity in the Valencia lake basin, which represents the core of the endemic area for schistosomiasis in Venezuela. Populations were sampled at short spatial scale (a few kilometres), both inside the lake and in ponds or rivers near the lake. Our results indicate that B. glabrata essentially cross-fertilizes, with little variation in selfing rates among populations. Our markers detected considerable genetic variation, with an average heterozygosity of 0.60. More diversity per population was found within than outside the lake, suggesting an influence of connectivity among populations on the levels of genetic diversity. A marked population structure was detected and lake populations were less structured than other populations. Most individuals were assigned to their population of origin using an assignment test. No strong demographic signal (e.g. bottleneck) was detected, though lake populations are likely to experience bottlenecks more frequently than the other populations analysed. Differences in gene flow therefore seem to play an important role in population differentiation and in the restoring of genetic diversity in demographically unstable populations.
Mol Ecol 2002 May
PMID:Fine-scale population structure and dispersal in Biomphalaria glabrata, the intermediate snail host of Schistosoma mansoni, in Venezuela. 1197 4

Schistosoma mansoni, a causative agent of schistosomiasis, is a major cause of human morbidity in tropical countries. Adult schistosomes, which reside in the hepatic portal system, are exposed to reactive oxygen compounds through respiration and as a result of the host immune response. To minimize oxidative stress schistosomes must possess adequate mechanisms of detoxification. Major detoxification systems rely on reducing equivalents from the disulfide oxidoreductases glutathione and thioredoxin. Therefore, maintenance of adequate levels of these thiols in a reduced form is critical. Here we show that S. mansoni possess an unusual thiol redox system centered on thioredoxin glutathione reductase. This enzyme represents an unusual fusion of a pyridine nucleotide disulfide oxidoreductase with a redox active glutaredoxin extension. Furthermore, we predict that this is a selenocysteine protein. Immunoprecipitation, western blot and inhibitor studies show that this protein has thioredoxin reductase, glutathione reductase, and glutaredoxin activities. Most importantly, we show that thioredoxin glutathione reductase appears to be the major, if not the sole enzyme for these activities in adult worms, completely replacing thioredoxin reductase and glutathione reductase. This is the first example of an organism with a redox system based exclusively on thioredoxin glutathione reductase.
Mol Biochem Parasitol 2002 Apr 30
PMID:The disulfide redox system of Schistosoma mansoni and the importance of a multifunctional enzyme, thioredoxin glutathione reductase. 1198 69

We studied the population genetic structure of 360 and 1247 adult Schistosoma mansoni using seven microsatellite and seven random amplified polymorphic DNA (RAPD) markers, respectively. Parasites were collected from their natural definitive host Rattus rattus in Guadeloupe (West Indies). We found a sex-specific genetic structure, a pattern never before reported in a parasitic organism. Male genotypes were more randomly distributed among rats than female genotypes. This interpretation was consistent with a lower differentiation between hosts for males relative to females, the higher genetic similarity between females in the same host and the observed local (i.e. within-individual-host) differences in allele frequencies between the two sexes. We discuss our results using ecological and immunological perspectives on host-parasite relationships. These results change our view on the epidemiology of schistosomiasis, a serious disease affecting humans in African and American intertropical zones.
Mol Ecol 2002 Jul
PMID:Sex-specific genetic structure in Schistosoma mansoni: evolutionary and epidemiological implications. 1207 30


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