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

The identification and characterization of a recombinant cDNA clone (OV103) expressing a microfilarial surface-associated antigen of Onchocerca volvulus is described. OV103 was identified and isolated from a lambda gt11 cDNA expression library derived from adult O. volvulus mRNA using a chimpanzee antiserum, taken 2 years after infection with third-stage larvae of O. volvulus. The cDNA clone encodes a 12.5-kDa protein that corresponds to a 15-kDa parasite protein present in microfilariae and adult female worms. The antigen encoded by this clone is located in the basal layer of the cuticle and the hypodermis of the female adult worm, and on the surface of microfilariae. OV103 fusion polypeptide is recognized only by some sera from onchocerciasis infected subjects (57%), but more significantly (89%) by sera from individuals that have low levels of patent infection. In addition, the antibody response to this protein developed before appearance of microfilariae in the skin of chimpanzees that had developed non-patent or low level patent infections, while the antibody response in chimpanzees with high levels of microfilariae appeared later at the time of appearance of microfilariae. Preliminary experiments indicated that affinity purified antibodies directed against OV103 fusion polypeptide mediated killing of nodular microfilariae in vitro in the presence of normal peripheral blood granulocytes.
Mol Biochem Parasitol 1992 Jan
PMID:Identification and characterization of an Onchocerca volvulus cDNA clone encoding a microfilarial surface-associated antigen. 154 18

Three new members of a developmentally regulated cysteine protease gene family of the parasitic nematode Haemonchus contortus have been isolated and characterized. One of the new genes, AC-3, was found to be linked in tandem to the previously characterized AC-2 gene. Nucleotide sequence analyses revealed that the first 90 amino acids of AC-3 are organized into four exons, similar to the situation in AC-2. A cDNA that appears to be a near full-length copy of the AC-3 gene was isolated using the polymerase chain reaction (PCR) technique to amplify cDNAs from adult worm poly(A)+ mRNAs. In addition to AC-3, a distinct cysteine protease cDNA, AC-4, was amplified by the same oligonucleotide primers. cDNAs encoding a fifth cysteine protease, AC-5, were isolated from an adult worm cDNA expression library using specific rabbit antisera and by PCR. Comparison of the predicted amino acid sequences of AC-3, AC-4 and AC-5 reveal that they share 64-77% identity with one another and with the previously reported AC-1 and AC-2 sequences. The amino acids surrounding the active site cysteine are highly conserved, as are the positions of other cysteine residues in the mature protein sequences. The H. contortus proteases are more similar to one another than they are to human cathepsin B (38-44% amino acid identity) or to the Sm31 cysteine protease of Schistosoma mansoni (36-40% identity). Our studies indicate that H. contortus adult worms express mRNAs for several distinct cysteine proteases. The significant primary sequence differences between the proteases suggest that they differ in their substrate specificities and precise physiological functions.
Mol Biochem Parasitol 1992 Apr
PMID:Cloning and sequence comparisons of four distinct cysteine proteases expressed by Haemonchus contortus adult worms. 157 79

Egg production by worm pairs is a major cause of pathogenesis in schistosomiasis. To further the understanding of female reproductive development, we have isolated and characterized a complete copy of an eggshell protein precursor gene, p48. Sequence analysis reveals that the gene has 3 open reading frames and does not contain an intron. One of the open reading frames, ORF1, encodes a polypeptide of 50 kDa which shows strong homology to insect chorion proteins. Determination of the position of the mRNA cap-site facilitated identification of putative regulatory elements in the 5' upstream region of the gene. Some of these elements (e.g., TCACGT) have been shown to play a role in the regulation of chorion gene expression in insects. p48 mRNA is detectable only in mature female worms and the ability to detect the mRNA coincides temporally with worm pairing. Quantitative comparisons, during female reproductive development, of p48 transcripts to those from another eggshell protein precursor gene, p14, show that the p48 mRNA is significantly less abundant than p14 mRNA. In mature female worms, p48 mRNA can only be detected in vitelline cells. Antibodies made against the polypeptide sequence deduced from ORF1 of the p48 gene recognize a 50-kDa molecule in extracts from mature female worms, but not in extracts from immature females or males.
Mol Biochem Parasitol 1992 May
PMID:Schistosoma mansoni p48 eggshell protein gene: characterization, developmentally regulated expression and comparison to the p14 eggshell protein gene. 162 6

We have recently demonstrated that a 200-kDa antigen that serves as a target of antibodies acting in synergy with praziquantel is linked to the surface membrane of Schistosoma mansoni by a glycosylphosphatidylinositol (GPI) anchor. In the present study we have examined the potential role of this GPI anchor in the therapeutic action of praziquantel by monitoring the release of surface antigens from living adult schistosomes cultured in the presence or absence of praziquantel and exogenous phospholipases. Phosphatidylinositol-specific phospholipase C (PIPLC) selectively released the 200-kDa antigen from the surface of adult schistosomes, as determined by immunoprecipitation experiments; none of the other GPI-anchored proteins, including alkaline phosphatase and a 22-kDa protein, were released by this enzyme. Anti-cross-reacting determinant antiserum (anti-CRD), which recognizes an epitope on GPI-anchored proteins only after the anchor has been removed by PIPLC, specifically precipitated the 200-kDa antigen, confirming the cleavage of its anchor. When the worms were exposed to both praziquantel and PIPLC, the amount of 200-kDa cleaved from the worms was increased five-fold. The selective release of this antigen was also detected by indirect immunofluorescent labeling of praziquantel-exposed adult worms cultured in the presence of phospholipases. Taken together these observations suggest that modulation of the phospholipase-mediated release of GPI-anchored antigens by praziquantel may contribute to the therapeutic action of the drug.
Mol Biochem Parasitol 1991 May
PMID:Selective release of a glycosylphosphatidylinositol-anchored antigen from the surface of Schistosoma mansoni. 164 1

Clones of the rRNA genes of Ostertagia ostertagi were selected from a library prepared from the genomic DNA of adult worms of strain LA-2. A 13.4-kb insert in a clone, lambda OOR78, is comprised of one complete 7.5-kb rDNA unit and portions of two adjacent units. The rDNA unit is directly repeated in a head-to-tail fashion and represents approximately 0.9% of the total genomic DNA. This repeating unit appears to be the only long tandemly repeated sequence in the genome. Restriction enzyme recognition sites in the rDNAs of four strains of O. ostertagi were fully conserved with the exception of one PstI site present in the large rRNA gene which was absent from a proportion of the genes of the LA-2 strain. The rDNA of O. ostertagi is more similar to that of Caenorhabditis elegans in unit length and arrangement than to parasitic helminths previously examined.
Mol Biochem Parasitol 1991 Apr
PMID:Cloning and characterization of the ribosomal RNA gene repeat from Ostertagia ostertagi. 167 20

Receptors potentially involved in neurotransmitting have been characterised in the muscle tissue and in whole worms of the nematodes Ascaris suum and Onchocerca volvulus, respectively. Binding studies revealed a high affinity for LSD with apparent KD values of 94 nM for A. suum and 120 nM for O. volvulus, whereas those of the neuroleptics haloperidol, spiperone and mianserin were found to be in the micromolar range. A variety of neurotransmitter antagonists, known to bind with high affinities either to mammalian D1/2 or to 5-HT1/2 receptors, were tested for their ability to bind to the nematode receptor. Results from these displacement experiments using tritiated LSD, mianserin, spiperone and haloperidol show distinct specificities of the nematode receptors compared to known receptor classes of mammals. With respect to this novel specificity, the nematode receptors seem to be unique and clearly distinct from those of the hosts.
Mol Biochem Parasitol 1991 Apr
PMID:Hallucinogenic and neuroleptic drug interactions with potential neurotransmitter receptors in parasitic nematodes. 167 21

The primary structure of an immunodominant antigen of the filarial parasite, Onchocerca volvulus was deduced from cDNA sequence analysis. Using affinity-purified antibody from onchocerciasis patients from West Africa, we have isolated a cDNA clone from a lambda gt11 cDNA expression library derived from microfilariae-producing female O. volvulus. The open reading frame encodes 152 amino acids, and the deduced sequence predicts a Mr of 16,850 (consistent with the apparent Mr of 18,000 of the immunoprecipitated in vitro translated product). The primary translation product contains a putative signal peptide of 16 amino acids. The mRNA coding for this antigen has an estimated size of 950 nucleotides. Furthermore, immunoelectron microscopy established that the antigen encoded by this clone is present in the hypodermis, the cuticle, and in the uterus of the filarial worms. Since this antigen is recognized exclusively by sera from onchocerciasis patients, and not by other sera from patients infected by other filarial parasites, it may prove to be an especially valuable tool for improving the specific diagnosis of onchocerciasis.
Mol Biochem Parasitol 1990 Feb
PMID:Identification of an Onchocerca volvulus cDNA encoding a low-molecular-weight antigen uniquely recognized by onchocerciasis patient sera. 168 59

Both Schistosoma japonicum and S. mansoni contain 28- and 26-kDa glutathione S-transferases (GSTs). Despite their immunological cross-reactivity using rabbit antisera, the S. japonicum 28-kDa GST (Sj28) is weakly immunogenic relative to the S. mansoni protein (Sm28) in mouse immunization experiments using GSTs purified from adult worms. The difference in immunogenicity is also observed during schistosome infection in mice. Using surface-labeled living S. japonicum worms, evidence was obtained for a surface location of Sj28 comparable to that reported for the S. mansoni molecule. The nucleotide and deduced amino acid sequences of cDNA clones corresponding to Sj28 and Sm28 were compared. Despite obvious homology (77% identity), differences were found in regions known to contain T epitopes in the S. mansoni protein which may be an explanation for the striking differences in immunogenicity in regard to antibody production in mice. The 26-kDa GSTs of these two parasites (Sj26 and Sm26) are also closely related on the basis of nucleotide and deduced amino acid sequences, there being 82% identity in the putative coding regions. When the amino acid sequences of Sj28 and Sm28 were compared with those of Sj26 and Sm26, the overall sequence identity was approximately 20%. However, a relatively conserved region was identified in otherwise structurally different molecules which may participate in common properties of these enzymes.
Mol Biochem Parasitol 1990 Apr
PMID:Comparison of the cloned genes of the 26- and 28-kilodalton glutathione S-transferases of Schistosoma japonicum and Schistosoma mansoni. 169 15

A polyclonal antiserum was raised to a gel purified preparation of the major water-soluble surface glycoprotein (gp29) of adult Brugia malayi, and used to define the stage specificity of expression, localisation (by immunoelectron microscopy) and the dynamics of biosynthesis and turnover via pulse-chase experiments. Gp29 was not detected in surface-labelled preparations of either pre- or post-parasitic third stage larvae (L3), but was present in fourth stage larvae (L4), where its mass was estimated to be 30 kDa by SDS-PAGE. In both L4 and adult worms, the protein resolved as 3 distinct species in 2-dimensional electrophoresis, with pIs from 6.5 to 7.5. Pulse-chase studies via metabolic labelling of adult worms with [35S]methionine in vitro indicated that gp29 was processed from a 32-kDa precursor to the mature molecule within 45 min and that it was secreted into culture medium within 5 h of synthesis. On extended culture, gp29 was converted to a 56-kDa product, presumably either by complex formation or covalent linkage with another secreted molecule. This higher molecular weight component had a more acidic pI of 4.5 and was insensitive to digestion with N-glycanase. Immunoelectron microscopy showed that gp29 was distributed throughout the cuticle and hypodermal cell layer of adult worms, suggesting that the protein was synthesised in the hypodermis, and that turnover into culture medium occurred through the cuticle. The protein appeared to concentrate at the distal cell membrane of the hypodermis, particularly at the stacked invaginations. Additional immunostaining was found on the basement membrane of the basal lamina of the intestine.
Mol Biochem Parasitol 1990 Aug
PMID:Cuticular localisation and turnover of the major surface glycoprotein (gp29) of adult Brugia malayi. 170 Feb 98

We have examined the expression of beta-tubulin genes in the parasitic nematode, Brugia pahangi. A genomic library was constructed and screened by hybridization with a Haemonchus contortus beta-tubulin cDNA fragment which recognizes several B. pahangi beta-tubulin sequences, including sequences which correspond to the previously characterized beta 1-tubulin gene. The B. pahangi beta 2-tubulin gene was isolated by selecting clones which hybridize to the H. contortus beta-tubulin gene but which do not hybridize to the beta 1-tubulin gene. A partial sequence of the beta 2-tubulin gene confirms that it codes for a distinct beta-tubulin. Southern hybridization analyses show that the beta 2-tubulin sequence exists as a single copy gene within the B. pahangi genome. Expression of the beta 2-tubulin gene is developmentally regulated and the message is found predominantly in adult male worms, whereas the beta 1-tubulin gene is expressed in microfilariae and approximately equal levels of the transcript are found in male and female adult worms. During mRNA maturation the beta 1-tubulin mRNA of microfilariae and adult worms acquires a trans-spliced leader identical to the SL1 of Caenorhabditis elegans.
Mol Biochem Parasitol 1992 Feb
PMID:Identification of a novel Brugia pahangi beta-tubulin gene (beta 2) and a 22-nucleotide spliced leader sequence on beta 1-tubulin mRNA. 174 Oct 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>