Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Here we describe three novel reactions of the self-splicing group II intron bI1 (the first intron of the COB gene of yeast mitochondria) demonstrating its catalytic versatility: reversal of the first step of the self-splicing reaction catalyzed by a linear form of the intron utilizing the energy of a phosphoanhydride bond for transesterification, ligation of a single-stranded DNA to an RNA, and cleavage of a single-stranded DNA substrate. These results have the following evolutionary implications: use of the alpha-beta bond of a terminal triphosphate for transesterification suggests that an RNA RNA replicase could use mononucleotide triphosphates as precursors, and cleavage of single-stranded DNA and DNA-RNA ligation suggests that excised group II introns might integrate directly into DNA without prior reverse transcription.
Cell 1992 Sep 04
PMID:New reactions catalyzed by a group II intron ribozyme with RNA and DNA substrates. 138 Dec 86

Studies from several laboratories have provided evidence that distinct stromal cell-derived signals are involved in the maturation of pre-B cells into surface Ig expressing B lymphocytes. In order to define the stage of development at which these stimuli act, various polymerase chain reaction strategies were used to characterize the status of kappa L chain gene rearrangements in nontransformed, stromal cell dependent pre-B cells. These cells were obtained from lymphoid colonies whose growth was potentiated by factors from a stromal cell line. kappa L chain genes in cells from many of these colonies were rearranged, and analysis of the Jk genes used indicated a bias toward the most 3' loci. However, the use of a reverse transcriptase PCR strategy failed to detect mature kappa transcripts, indicating that stromal cell mediators exist that allow pre-B cells to progress to the stage at which L chain genes are rearranged but not expressed. Reverse transcriptase PCR further revealed that no transcripts for c-kit (the receptor for kit-ligand) and the IL-7R could be detected in these cells. This suggests that these receptors are no longer expressed by the time cells have undergone kappa rearrangements and minimize a role for stromal cell-derived kit-ligand and IL-7 in mediating the pre-B to B cell transition.
J Immunol 1992 Sep 15
PMID:Status of kappa L chain gene rearrangements and c-kit and IL-7 receptor expression in stromal cell-dependent pre-B cells. 138 91

The complete 5284-nucleotide sequence of the double-stranded RNA genome of Leishmania RNA virus 1 (LRV1) was determined and contains three open reading frames (ORFs) on the plus (+) (mRNA) strand. The predicted amino acid sequence of ORF3 has motifs characteristic of viral RNA-dependent RNA polymerases. ORF2, which may encode the major viral coat protein, overlaps ORF3 by 71 nucleotides, suggesting a +1 translational frameshift to produce a gag-pol type of fusion protein. Two alternative models for the frameshift are presented. The 5' splice leader sequence of kinetoplastid mRNAs is not in LRV1 RNA. This suggests that the 450-base region at the 5' end of the LRV1 (+)-strand, which contains ORF1 and is highly conserved among viral strains, does not encode protein but has a role in initiation of translation and/or RNA stability. The similarity of LRV1 genomic organization, replication cycle, and RNA-dependent RNA polymerase sequence to those of the yeast virus ScV L-A suggests a common ancestral origin. The possibility that LRV1 affects pathogenesis in leishmaniasis is intriguing.
Proc Natl Acad Sci U S A 1992 Sep 15
PMID:Molecular organization of Leishmania RNA virus 1. 138 95

Transcription factors containing the POU-domain have been shown to be important regulators of tissue-specific gene expression in the pituitary and lymphoid cells. Using a polymerase chain reaction (PCR)-based strategy, we have searched for similar factors that may be expressed in adult human pancreatic islets. This approach resulted in the amplification of sequences encoding the octamer binding proteins Oct1 and Oct3 (also called Oct4). The isolation of cDNAs encoding Oct3 revealed the expression of two isoforms of this transcription factor termed Oct3A and Oct3B that are generated by alternative splicing. Human Oct3A and Oct3B are composed of 360 and 265 amino acids, respectively, of which the 225 amino acids at the COOH-termini are identical. The sequence of human Oct3A shows 87% amino acid identity with mouse Oct3. Reverse-transcriptase PCR showed low levels of expression of both Oct3A and Oct3B mRNA in all adult human tissues examined. We also isolated and characterized the human Oct3 gene (OTF3) and a related gene, OTF3C. The human Oct3 gene, localized to human chromosome 6 in the region of the MHC complex, spans about 7 kb and consists of five exons. The Oct3-related gene, OTF3C, is a retroposon and has been localized to human chromosome 8. Southern blotting and PCR amplification of human DNA indicated the presence of other OTF3-related genes as has been previously noted in the mouse. Two polymorphisms which can be typed using PCR were identified in OTF3 which will facilitate genetic studies of this gene.
Nucleic Acids Res 1992 Sep 11
PMID:Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues. 140 63

Twenty six patients with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) treated with IFN-alpha were classified on the basis of the fusion pattern of BCR/ABL chimeric mRNA determined by a reverse-transcriptase-polymerase chain reaction (RT-PCR) method. The relationship between the fusion pattern of BCR/ABL mRNA and the clinical outcome was also analysed. Twelve patients showed M-bcr exon 3/ABL exon 2 (B3/A2) chimeric mRNA and nine had M-bcr exon 2/ABL exon 2 (B2/A2) mRNA. Eleven of the 12 patients with B3/A2 achieved complete hematological response with IFN-alpha therapy, as did three of the nine patients with B2/A2. The mean duration to blastic crisis was significantly longer in the B3/A2 patients (mean 52.4 months) than in the B2/A2 patients (mean 26.2 months) (p less than 0.01). These results suggest that the fusion pattern of BCR/ABL mRNA may affect the therapeutic response to IFN-alpha and clinical outcome in CML patients.
Leukemia 1992 Sep
PMID:Possible correlation between fusion pattern of BCR/ABL mRNA and clinical response to alpha-interferon in chronic myelogenous leukemia. 151 6

Computer-assisted comparison of the nonstructural polyprotein of hepatitis E virus (HEV) with proteins of other positive-strand RNA viruses allowed the identification of the following putative functional domains: (i) RNA-dependent RNA polymerase, (ii) RNA helicase, (iii) methyltransferase, (iv) a domain of unknown function ("X" domain) flanking the papain-like protease domains in the polyproteins of animal positive-strand RNA viruses, and (v) papain-like cysteine protease domain distantly related to the putative papain-like protease of rubella virus (RubV). Comparative analysis of the polymerase and helicase sequences of positive-strand RNA viruses belonging to the so-called "alpha-like" supergroup revealed grouping between HEV, RubV, and beet necrotic yellow vein virus (BNYVV), a plant furovirus. Two additional domains have been identified: one showed significant conservation between HEV, RubV, and BNYVV, and the other showed conservation specifically between HEV and RubV. The large nonstructural proteins of HEV, RubV, and BNYVV retained similar domain organization, with the exceptions of relocation of the putative protease domain in HEV as compared to RubV and the absence of the protease and X domains in BNYVV. These observations show that HEV, RubV, and BNYVV encompass partially conserved arrays of distinctive putative functional domains, suggesting that these viruses constitute a distinct monophyletic group within the alpha-like supergroup of positive-strand RNA viruses.
Proc Natl Acad Sci U S A 1992 Sep 01
PMID:Computer-assisted assignment of functional domains in the nonstructural polyprotein of hepatitis E virus: delineation of an additional group of positive-strand RNA plant and animal viruses. 151 55

We have determined the complete nucleotide sequence of the largest segment S1 of rice dwarf phytoreovirus (RDV), a member of the family Reoviridae. S1 is 4423 nucleotides long with a segment-specific inverted repeat located adjacent to the conserved termini (5'GGCAAA---UGAU3'). A major open reading frame (bases 36 to 4367) on the S1 plus strand, which is preceded by a minicistron (bases 6 to 29), encodes the polypeptide (P1) consisting of 1444 amino acids with a M(r) of 164, 142. The sense-strand transcript derived from the full-length S1 cDNA, the minicistron of which was abolished, directed the synthesis of a polypeptide of 170 kDa in addition to smaller polypeptides in wheat germ extracts, and the 170-kDa product comigrated with the minor core protein in SDS-polyacrylamide gel. Thus, P1 is assumed to be localized in the viral core particle. The consensus sequence element conserved in RNA-dependent RNA polymerase is observed in the P1 amino acid sequence predicted from the nucleotide sequence. Based on the dendrogram established from the sequence alignment around the polymerase module region, and sequence identity within the alignment, P1 of plant-infecting RDV was evolutionarily compared with VP1, lambda 3, and VP1 of three other animal-infecting members of the family, rota-, reo-, and bluetongue viruses. Consequently, RDV S1 was shown to be more closely related to the rotavirus gene segment 1, in terms of molecular evolution, than the animal-infecting members are to one another.
Virology 1992 Sep
PMID:Molecular analysis of rice dwarf phytoreovirus segment S1: interviral homology of the putative RNA-dependent RNA polymerase between plant- and animal-infecting reoviruses. 152 32

RNA-dependent RNA polymerases contain a highly conserved region of amino acids with a core segment composed of the amino acids YGDD which have been hypothesized to be at or near the catalytic active site of the molecule. Six mutations in this conserved YGDD region of the poliovirus RNA-dependent RNA polymerase were made by using oligonucleotide site-directed DNA mutagenesis of the poliovirus cDNA to substitute A, C, M, P, S, or V for the amino acid G. The mutant polymerase genes were expressed in Escherichia coli, and the purified RNA polymerases were tested for in vitro enzyme activity. Two of the mutant RNA polymerases (those in which the glycine residue was replaced with alanine or serine) exhibited in vitro enzymatic activity ranging from 5 to 20% of wild-type activity, while the remaining mutant RNA polymerases were inactive. Alterations in the in vitro reaction conditions by modification of temperature, metal ion concentration, or pH resulted in no significant differences in the activities of the mutant RNA polymerases relative to that of the wild-type enzyme. An antipeptide antibody directed against the wild-type core amino acid segment containing the YGDD region of the poliovirus polymerase reacted with the wild-type recombinant RNA polymerase and to a limited extent with the two enzymatically active mutant polymerases; the antipeptide antibody did not react with the mutant RNA polymerases which did not have in vitro enzyme activity. These results are discussed in the context of secondary-structure predictions for the core segment containing the conserved YGDD amino acids in the poliovirus RNA polymerase.
J Virol 1991 Sep
PMID:Enzymatic activity of poliovirus RNA polymerase mutants with single amino acid changes in the conserved YGDD amino acid motif. 165 2

All the forms of 3C protease previously found were isolated and purified. A 3D polymerase's fragment covalently bound with 3C protein does not affect the specific proteolytic activity of the enzyme, whereas the elimination of 26 N-terminal amino acid residues of 3C protease leads to its inactivation.
Bioorg Khim 1991 Sep
PMID:[Isolation and purification of 3C-proteinase from the poliomyelitis virus. Identification of an active form of the enzyme]. 166 50

Reverse transcriptase (RT) plays an essential role in the life cycle of the human immunodeficiency viruses (HIV). A better understanding of this enzyme, and its two catalytic functions, the DNA polymerase and the RNase H, could lead to the development of new drugs that would specifically block HIV replication. The available genetic, sequence, biochemical, and immunological data on the reverse transcriptase of HIV-1 constrain the possible structure of the DNA polymerase domain. The purpose of this review is to correlate the data and to discuss, in light of that data, a model for the structure of the polymerase domain. In this model, the polymerase domain is approximately 50 to 60 A in diameter with a 20 A opening to accommodate the nucleic acid duplex. The most evolutionarily conserved region of RT (amino acids 20-190 of HIV-1 RT) is proposed to form the inner surface of the 20 A opening to which the nucleic acid hemiduplex is bound.
AIDS Res Hum Retroviruses 1990 Sep
PMID:HIV-1 reverse transcriptase: structure predictions for the polymerase domain. 170 98


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