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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oncogene GLI is amplified and expressed in some cases of human malignant glioma and undifferentiated childhood sarcoma and is the prototype for a gene family characterized by a highly conserved set of five tandem zinc fingers and a consensus cysteine-histidine link. This zinc finger motif has been shown to bind DNA with sequence specificity and may mediate transcriptional regulation. Since GLI is expressed in embryonal carcinoma cell lines but not in most normal adult tissues and shows significant sequence similarity within its zinc finger domain to cubitus interruptus dominant (ciD), a Drosophila segmentation gene known to be important in the morphogenesis of the posterior portion of each larval segment, we established the temporal and tissue expression patterns of the mouse homologue of human GLI in day 10 through 18 mouse embryos with Northern blotting, reverse transcriptase coupled PCR, and in situ hybridization. gli transcripts were demonstrated on days 10 through 18 of mouse embryonic development as well as in normal adult uterus, brain, testis, and limb. Tissue expression of gli during gestation was demonstrated in Meckel's precartilage mesenchyme, the basis occipitus, rib mesenchymal condensations, primordial vertebral bodies, digital mesenchymal condensations in forefoot and hindfoot plates, the ependymal layer of the spinal cord, and the mesoderm of the gastrointestinal tract. Expression persisted throughout gestation in developing bone and cartilage of the extremities, the ribs, and the vertebral bodies, as well as the gastrointestinal tract mesoderm. These findings support a role for gli family genes in normal craniofacial and digital development in mammals first suggested by the demonstration of translocation breakpoints within the GLI3 gene in families with the Greig cephalopolysyndactylyl syndrome and subsequently by reduced gli3 expression in the mouse mutant extra toes. It is surprising that a single gene would be expressed in such a wide range of mesenchymal structures.
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PMID:gli, a zinc finger transcription factor and oncogene, is expressed during normal mouse development. 836 25

Nineteen recombinant phages containing DNA from the region of Balbiani ring a (BRa), which develops on chromosome IV in cells of the special lobe of the Chironomus thummi salivary gland, were isolated from a Chironomus thummi genomic library. Three of the clones contained transposable element sequences that hybridized to more than 100 sites on all four Chironomus chromosomes, including constant and variable sites. Two handogous clones, lambda 24 (which lacks the transposable element) and lambda 43 (which contains this insertion) were investigated by nucleotide sequence analysis. The complete nucleotide sequence of the 4.8 kb transposable element from Chironomus thummi (NLR1Cth) is reported here. This element contains two overlapping open reading frames of 1887 (ORF1) and 2649 bp (ORF2). Three cysteine motifs are found in the sequence of ORF1. Sequence similarity was found between ORF2 and known genes of viruses and transposable elements which encode reverse transcriptase. The NLR1Cth element has no long terminal repeats and is flanked by short direct repeats of the sequence TATCACTGACAAC. A 24 bp poly(dA) sequence was found at the 3' end of the element. Based upon its structural organization and comparative analysis of its nucleotide sequence we suggest that this NLR1Cth element belongs to the class of non-LTR retrotransposons. The genomic clone pC6.10 was previously obtained by microdissection and cloning of DNA from polytene chromosome IV of Chironomus thummi. A 2.4 kb insertion contained part of the 3' terminal region of the NLR1Cth element, but this differed in sequence from the first copy by several nucleotide substitutions and a shorter poly (dA) tract at the 3' end.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The Chironomus thummi genome contains a non-LTR retrotransposon. 838 52

Aurothioglucose and aurothiomalate have anti-HIV-1 activity in vitro. Antiviral activity requires the formation of a reactive intermediate with a molar equivalent amount of a thiol ligand. This activates gold(I) ligand exchange between the reactive species bis(thiolato)gold(I) and acidic thiol groups exposed on the surface of proteins. Bis(thioglucose)gold(I) (bisAuTG) which is formed by the reaction of molar equivalent amounts of aurothioglucose and 1-thio-beta-D-glucose completely protected MT-4 and CEM cells against HIV-1NL4-3-induced cytopathogenicity. Although bisAuTG is an inhibitor of human immunodeficiency virus-1 (HIV-1) reverse transcriptase in a cell-free assay, its antiviral effect is due to modification of a surface component of the virion. The HIV-1 strain NL4-3 is 200-fold more sensitive to inhibition of infectivity by bisAuTG than are the strains MN, RF, and SF-2. HIV-1NL4-3 has a unique cysteine residue close to the amino terminus of its gp41 envelope glycoprotein (residue 532 of gp160) which we hypothesize is the target of bisAuTG binding. Mutation of that residue alters HIV-1NL4-3 infectivity and dominantly suppresses virus assembly when coexpressed with the wild-type NL4-3 genome. We show that bisAuTG treatment releases gp120 from the surface of cells expressing wild-type HIV-1NL4-3 envelope glycoprotein, but it does not release gp120 if Cys532 is mutationally altered to Ala. Thus, the antiviral effect of bisAuTG on HIV-1NL4-3 is due to an effect on the association of gp120 with gp41.
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PMID:Aurothiolates inhibit HIV-1 infectivity by gold(I) ligand exchange with a component of the virion surface. 842 3

A cDNA encoding 57 kDa and 53 kDa antigens (MGP57/53) recognized by monoclonal antibodies raised against bovine milk fat globule membrane (MFGM) (Biochim. Biophys. Acta 1199 (1994) 87-95) was cloned from lactating bovine mammary gland by a combination of reverse transcriptase-coupled polymerase chain reaction (RT-PCR) and 3'-rapid amplification of cDNA ends (3'-RACE). The deduced amino-acid sequence showed that mature MGP57/53 consists of 409 amino-acid residues and the calculated molecular weight and isoelectric point are 45,544 and 6.42, respectively. Computer analysis reveals that it has a significant similarity to mouse mammary epithelial cell surface protein, MFG-E8 and a human breast tumor-associated glycoprotein antigen, BA46-1. An N-terminal cysteine-rich domain and a C-terminal tandemly repeated sequence were highly conserved among them, but bovine MGP57/53 lacks 36 amino-acid residues containing a cluster of 5 prolines found in mouse MFG-E8. Northern blot analysis showed that the cDNA hybridized to about 2.0 kb mRNA of lactating bovine mammary gland. These results strongly support our previous report that the two MFGM antigens originate from a single gene and are isoforms with different N-linked sugar chains.
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PMID:Molecular cloning of glycoprotein antigens MGP57/53 recognized by monoclonal antibodies raised against bovine milk fat globule membrane. 854 16

The parameters governing the polymerization mechanism of reverse transcriptase containing the tyrosine to cysteine mutation at position 181 (Y181C) were determined using pre-steady-state techniques. The pathway for single nucleotide incorporation catalyzed by Y181C is similar to that determined for wild-type RT where a rate-limiting conformational change precedes fast chemistry and is followed by slow steady-state release of the primer/template. The Y181C mutant enzyme binds a 25/45-mer duplex DNA tightly with a Kd of 11 nM. However, the Y181C mutation weakens the nucleotide affinity 2-3-fold relative to the wild-type complex. We also determined the parameters governing the mechanism of nonnucleoside inhibitor resistance with Y181C. The Kd value of Nevirapine with the mutant E.DNA complex increased approximately 500-fold. The decreased affinity of Nevirapine for the mutant enzyme is a consequence of a faster inhibitor dissociation rate from the enzyme complex of Y181C relative to that of the wild-type. The E.DNA complex of Y181C may be saturated with Nevirapine, and the I.E.DNA complex is capable of a maximum incorporation rate of 0.1 s-1 (a 10-fold faster rate than that of the wild-type I.E.DNA complex). The overall two-step binding of nucleotide to Y181C in the presence of Nevirapine remains unaffected.
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PMID:HIV-1 reverse transcriptase resistance to nonnucleoside inhibitors. 854 41

The cattle protozoan parasite Tritrichomonas foetus has multiple forms of cysteine proteinases. To investigate their diversity, PCR and reverse transcriptase PCR were used to isolate genomic DNA and cDNA fragments, respectively, encoding different cysteine proteinases. Seven genes have been identified, TFCP3-6 from amplification of genomic DNA and TFCP7-9 from amplification of cDNA. Comparison of the predicted amino acid sequences indicates that the T. foetus enzymes are cathepsin-L-like rather than cathepsin-B-like in structure. However, there is considerable diversity among the proteinases. TFCP7 and TFCP8 are most similar to one another (78% identity), while TFCP3 and TFCP9 are the least closely related (30% identity). All but one of the genes are single-copy, the exception being TFCP3, which was present in multiple copies in one of the three isolates examined. Single transcripts were detected for each of the seven genes. TFCP8 was expressed at the highest levels, while transcripts for TFCP4 were only just detectable. In T. foetus F2, the strain from which the genomic DNA and mRNA were isolated, transcripts of the five other genes were present at intermediate levels. When two other isolates were compared with F2, differences in the expression of individual genes were apparent, with either one or two of them not expressed. In spite of these differences the major cysteine proteinases detected in the three isolates using substrate-SDS-PAGE appeared identical. The data show that the multiplicity of cysteine proteinases in T. foetus is due, in part at least, to the presence of multiple genes and that some of the genes encode cysteine proteinases which are not among the high-activity enzymes detected previously.
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PMID:Multiple cysteine proteinases of the pathogenic protozoon Tritrichomonas foetus: identification of seven diverse and differentially expressed genes. 857 1

Complement C4 shows extensive structural and functional similarity to complement C3, hence these components are believed to have originated by gene duplication from a common ancestor. Although to date C3 cDNA clones have been isolated from all major classes of extant vertebrates including Xenopus, C4 cDNA clones have been isolated from mammalian species only. We describe here the molecular cloning and structural analysis of Xenopus C4 cDNA. The cDNA sequence encoding the thioester region of Xenopus C4 was amplified by reverse transcriptase-polymerase chain reaction using Xenopus liver mRNA as a template, and then used to screen a liver cDNA library. The amino acid sequence of Xenopus C4 deduced from a clone containing the entire protein-coding sequence showed 39%, 30%, 25%, and 20% overall identity with those of human C4, C3, C5, and alpha2-macroglobulin, respectively. The predicted amino acid sequence consisted of a 22-residue putative signal peptide, a 634-residue beta chain, a 732-residue alpha chain, and a 287-residue gamma chain. Of 30 cysteine residues, 27 were found in exactly the same positions as in human C4. Genomic Southern blotting analysis indicated that C4 is a single copy gene in Xenopus and is part of the frog MHC cluster. These results clearly demonstrate that C3/C4 gene duplication and linkage between the C4 gene and the major histocompatibility complex predate mammalian/amphibian divergence.
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PMID:Fourth component of Xenopus laevis complement: cDNA cloning and linkage analysis of the frog MHC. 860 56

Human immunodeficiency virus type 1 (HIV-1)-infected CEM cells were treated (as single agents or in combination) with (minus)-2', 3'-dideoxy-3'-thiacytidine (3TC) and the following HIV-1-specific non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs): 2', 5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5'-(4'-amino-1',2'-oxathi ole)-2',2'-dioxide derivative of 3-methylthymidine (TSAO-m3T), the thiocarboxanilides UC10 and UC42, bis(heteroaryl)piperazine (BHAP) derivative U90152, and the 1-(2-hydroxyethoxymethyl)-6-(phenylthio)thymine (HEPT) derivative 5-isopropyl-1-ethoxymethyl-6-benzyluracil (MKC-442). When used individually, the compounds led to the emergence of HIV-1 strains containing the following mutations in the RT: Glu138 to lysine for TSAO-m3T, Met184 to valine for 3TC, Lys103 to threonine/asparagine for the thiocarboxanilides, and Tyr181 to cysteine for BHAP and MKC-442. When 3TC was combined with TSAO-m3T, UC10, UC42, BHAP, or MKC-442, breakthrough of virus was markedly delayed or even suppressed. For these drug combinations, the concentrations of the individual drugs could be lowered by > or = 25-50-fold to suppress virus breakthrough compared with the individual use of the compounds. The concomitant presence of the Lys138 and Ile/Val184 mutations was found in the RT of the mutant viruses that emerged with combination therapy of the lowest concentrations of 3TC with either the lowest concentrations of TSAO-m3T or UC10 (approximately 0.5-3-fold the EC50 value). These virus strains retained high sensitivity to other NNRTIs such as BHAP or HEPT. The virus mutants that arose in the presence of combinations of the lowest concentrations of 3TC with either BHAP or HEPT predominantly contained the Cys181 mutation in the RT. In one case, the Ile181 mutation was found. The latter mutations, particularly the Ile181 mutation, resulted in markedly decreased sensitivity to the NNRTIs but not to 3'-azido-2', 3'-dideoxythymidine or 3TC.
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PMID:Marked inhibitory activity of non-nucleoside reverse transcriptase inhibitors against human immunodeficiency virus type 1 when combined with (-)2',3'-dideoxy-3'-thiacytidine. 862 38

In an earlier study on minus-strand DNA synthesis catalyzed by murine leukemia virus reverse transcriptase, we described a prominent pause site near the polypurine tract (J. Guo, W. Wu, Z. Y. Yuan, K. Post, R. J. Crouch, and J. G . Levin, Biochemistry 34:5018-5029, 1995). We now report that pausing at this site is due to a stem-loop structure in the RNA template, formed by interaction of a number of bases in the polypurine tract, including the six G's, and a 3' sequence which includes four C's. Addition of human immunodeficiency virus type 1 (HIV-1) nucleocapsid (NC) protein to reverse transcriptase reactions reduces pausing by approximately 8- to 10-fold and stimulates synthesis of full-length DNA. Thus, NC functions as an accessory protein during elongation of minus-strand DNA and increases the efficiency of DNA synthesis, in this case, by apparently destabilizing a region of secondary structure in the template. Since NC is associated with genomic RNA in the viral core and is likely to be part of a viral replication complex, these results suggest that NC may also promote efficient DNA synthesis during virus replication. Mutational analysis indicates that the features of HIV-1 NC which are important for reduction of pausing include the basic amino acids flanking the first zinc finger, the zinc fingers, and the cysteine and aromatic amino acids within the fingers. These findings suggest that reverse transcription might be targeted by drugs which inactivate the zinc fingers of HIV-1 NC.
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PMID:Human immunodeficiency virus type 1 nucleocapsid protein reduces reverse transcriptase pausing at a secondary structure near the murine leukemia virus polypurine tract. 879 60

The primary sequence of the prolactin receptor (PRL-R) in turkeys was deduced from a cDNA clone isolated from a kidney cDNA library and from a polymerase chain reaction (PCR) product. The open reading frame of the turkey PRL-R (tPRL-R) predicted an 831-amino acid protein composed of a leader peptide, an extracellular domain, a single transmembrane domain, and an intracellular domain. The extracellular domain contained two homologous repeat units with 63% amino acid sequence identity to each other. Each repeat unit contained all of the conserved cysteine pairs and a WSXWS motif found in mammalian PRL-Rs. A tPRL-R transcript with a molecular size of about 3000 nucleotides was identified by Northern blot analysis. The tPRL-R transcripts were detected in all 26 tissues examined using reverse transcriptase PCR (RT-PCR). The pituitary gland, hypothalamus, crop sac, duodenum, and gizzard were found to express the highest levels of tPRL-R among the 26 tissues. The expression levels of tPRL-R in 17 tissues were compared using semi-quantitative RT-PCR in nonphotostimulated, laying, out-of-lay, incubating, and maternal hens, and male birds. In most tissues examined there was no obvious relationship between blood levels of PRL, reproductive states, and estimated concentrations of the receptor mRNA. In the pituitary gland and hypothalamus, plasma levels of PRL and levels of tPRL-R transcript were inversely correlated. In the hypothalamus, increasing blood levels of PRL were associated with decreasing levels of the receptor transcript (p < or = 0.05), whereas the opposite was observed in the pituitary gland (p < or = 0.05). These findings support the hypothesis that PRL itself may participate in the neuroendocrine control of incubation behavior through actions on both the hypothalamus via a short-loop feedback mechanism and the pituitary gland via autocrine and/or paracrine effects.
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PMID:Molecular cloning, tissue distribution, and expression of the prolactin receptor during various reproductive states in Meleagris gallopavo. 890 21


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