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:1.1.1.1 (alcohol dehydrogenase)
9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MOD5, a nuclear gene of Saccharomyces cerevisiae, encodes two isozymic forms of a tRNA-modification enzyme. These enzymes modify both cytoplasmic and mitochondrial tRNAs. Two inframe ATGs of the MOD5 gene are used for initiation of translation, and the form of the protein translated from the first AUG is imported into mitochondria. Protein translated from the second AUG functions in the cytoplasm. Since all transcripts contain both of these translational start sites and two proteins are made, the question arises as to the factors that influence the translation start-site choice. Extending the 5' ends of the MOD5 mRNA to include leader sequences of the ADH1 (alcohol dehydrogenase defective) transcript produces significant changes in the choice of AUGs. This suggests that for wild-type MOD5 transcripts, the length or structure of the leader sequence plays a role in AUG choice. The nucleotides surrounding the first ATG of MOD5 also have an effect on translation initiation. Altering these nucleotides changes initiation choice and suggests that ribosomal bypass of a suboptimal AUG is another mechanism controlling the alternate use of two initiation codons. Our data support the model that at least one MOD5 transcript is able to produce two proteins with different N-terminal sequences.
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PMID:mRNA leader length and initiation codon context determine alternative AUG selection for the yeast gene MOD5. 194 3

Amber (UAG) and opal (UGA) nonsense suppressors were constructed by oligonucleotide site-directed mutagenesis of two Drosophila melanogaster leucine-tRNA genes and tested in yeast, Drosophila tissue culture cells and transformed flies. Suppression of a variety of amber and opal alleles occurs in yeast. In Drosophila tissue culture cells, the mutant tRNAs suppress hsp70:Adh (alcohol dehydrogenase) amber and opal alleles as well as an hsp70:beta-gal (beta-galactosidase) amber allele. The mutant tRNAs were also introduced into the Drosophila genome by P element-mediated transformation. No measurable suppression was seen in histochemical assays for Adhn4 (amber), AdhnB (opal), or an amber allele of beta-galactosidase. Low levels of suppression (approximately 0.1-0.5% of wild type) were detected using an hsp70:cat (chloramphenicol acetyltransferase) amber mutation. Dominant male sterility was consistently associated with the presence of the amber suppressors.
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PMID:Drosophila nonsense suppressors: functional analysis in Saccharomyces cerevisiae, Drosophila tissue culture cells and Drosophila melanogaster. 217 93

We have sequenced Bs1, an insertion element isolated from a null allele of the Adh1 locus encoding alcohol dehydrogenase in maize. The Bs1 element is 3203 base pairs (bp) in length, has 302-bp identical long terminal direct repeats (LTRs), and created a 5-bp flanking direct duplication of target Adh1 DNA upon insertion. The 5' LTR is followed by a canonical primer binding site with homology to the plant initiator methionyl-tRNA, and the 3' LTR is directly preceded by a polypurine stretch like that observed in retroviruses and retrotransposons. Bs1 encodes two overlapping open reading frames specifying peptides of 740 and 168 amino acids. The longer open reading frame specifies a peptide with amino acid homology to the protease and nucleic acid binding moiety of retroviruses and retrotransposons. The deduced amino acid sequence encoded by Bs1 lacks convincing homology to the polymerase (reverse transcriptase) encoded by retroposons, despite the fact that this polymerase-encoding domain is routinely the most conserved region of any such element. The sequence and relatively small size of Bs1 suggest that this element is a deleted retrotransposon that inserted into Adh1 with the aid of a reverse transcriptase function provided in trans. In vitro transcribed Bs1 complementary RNA was translated in vitro to produce both a protein of 81 kDa representing open reading frame 1 (ORF1) and one of the 95-kDa size predicted for the frame-shifted fusion of ORF1 and ORF2. As with many other retroposons, the efficiency of translational initiation at the AUG beginning ORF1 was not noticeably affected by the presence of one or more upstream, unproductive AUGs in the complementary RNA transcript.
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PMID:Structure and coding properties of Bs1, a maize retrovirus-like transposon. 247 29

We have characterized a nonsense mutation in the ADR1 gene that identifies the translational start of the ADR1 protein. The ADR1 gene of Saccharomyces cerevisiae is required for synthesis of the glucose-repressible alcohol dehydrogenase (ADH2). The adr1-1 mutation, which inhibits ADH2 expression, was identified as a C to G transversion at base pair +32. This alteration would result in a UGA nonsense codon in place of a serine codon that would lead to termination of the ADR1 polypeptide after the 10th amino acid. The effect of the adr1-1 mutation was partially reversed by UGA-tRNA suppressors, indicating that the adr1-1 mutation affects ADR1 expression at the translational level. These observations establish that the first available AUG in the ADR1 sequence is used as the translational start site of ADR1. Tyrosine or leucine UGA-tRNA-suppressors resulted in levels of adr1-1 activity similar to that found for a serine UGA-tRNA-suppressor, suggesting that serine residue-11 is not essential to ADR1 function. Northern analyses showed that the 5.1 kb ADR1 mRNA was two- to three-fold more abundant when isolated from a strain carrying the ADR1 allele than from an isogenic strain containing the adr1-1 allele. These data confirm that the 5.1 kb mRNA is the ADR1 mRNA and suggest that inhibition of adr1-1 mRNA translation results in more rapid degradation of the adr1-1 mRNA.
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PMID:Characterization of the adr1-1 nonsense mutation identifies the translational start of the yeast transcriptional activator ADR1. 267 89

When RNA isolated from the Drosophila melanogaster alcohol dehydrogenase (ADH) negative mutant CyOnB was translated "in vitro" in the presence of yeast opal suppressor tRNA, a wild type size ADH protein was obtained in addition to the mutant gene product. This identifies the CyOnB mutant as an opal (UGA) nonsense mutant. From the molecular weight of the mutant protein, and from the known sequence of the ADH gene (Benyajati et al., Proc.Natl.Acad.Sci. USA 78, 2717-2721, 1981), we conclude that the tryptophan codon UGG in position 234 has been changed into a UGA nonsense codon in the CyOnB mutant. Furthermore, we show that the UAA stop codon of the wild type ADH gene is resistant to suppression by a yeast ochre suppressor tRNA. This is in contrast to the high efficiency of suppression of the CyOnB UGA nonsense codon, despite an almost identical codon context.
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PMID:In vitro suppression of a nonsense mutant of Drosophila melanogaster. 681 27

Poly(A+)-containing mRNA from human term placenta was used to direct protein synthesis in a nuclease-treated rabbit reticulocyte lysate, which is dependent on mRNA and tRNA for maximal activity. The major protein product was human pre-placental lactogen (hPL). Addition of tRNA from rabbit liver, rabbit reticulocyte, human first trimester and term placenta, human liver and yeast resulted in 2-5-fold stimulation of [35S]methionine incorporation into total protein. Although all mammalian tRNA increased hPL synthesis, the relative synthesis as compared to endogenous globin was markedly different and most efficient with tRNA from term placenta. Addition of yeast tRNA increased total incorporation 3-fold but decreased incorporation of [35S]methionine into pre-hPL. These results suggest that the population of isoacceptor tRNAs may influence the expression of hPL in term placenta. Results are discussed by showing codon bias and usage of mRNA coding for hPL, alpha- and beta-hCG, rabbit globin and yeast alcohol dehydrogenase I.
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PMID:Effect of transfer RNA from various sources on placental messenger RNA translation. 683 70

Extreme codon bias is seen for the Saccharomyces cerevisiae genes for the fermentative alcohol dehydrogenase isozyme I (ADH-I) and glyceraldehyde-3-phosphate dehydrogenase. Over 98% of the 1004 amino acid residues analyzed by DNA sequencing are coded for by a select 25 of the 61 possible coding triplets. These preferred codons tend to be highly homologous to the anticodons of the major yeast isoacceptor tRNA species. Codons which necessitate site by side GC base pairs between the codons and the tRNA anticodons are always avoided whenever possible. Codons containing 100% G, C, A, U, GC, or AU are also avoided. This provides for approximately equivalent codon-anticodon binding energies for all preferred triplets. All sequenced yeast genes show a distinct preference for these same 25 codons. The degree of preference varies from greater than 90% for glyceraldehyde-3-phosphate dehydrogenase and ADH-I to less than 20% for iso-2 cytochrome c. The degree of bias for these 25 preferred triplets in each gene is correlated with the level of its mRNA in the cytoplasm. Genes which are strongly expressed are more biased than genes with a lower level of expression. A similar phenomenon is observed in the codon preferences of highly expressed genes in Escherichia coli. High levels of gene expression are well correlated with high levels of codon bias toward 22 of the 61 coding triplets. As in yeast, these preferred codons are highly complementary to the major cellular isoacceptor tRNA species. In at least four cases (Ala, Arg, Leu, and Val), these preferred E. coli codons are incompatible with the preferred yeast codons.
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PMID:Codon selection in yeast. 703 77

We have determined the extent to which acute ethanol administration perturbs the synthesis of ventricular contractile and non-contractile proteins in vivo. Male Wistar rats were treated with a standard dose of ethanol (75 mmol kg-1 body weight; i.p.). Controls were treated with isovolumetric amounts of saline (0.15 mol l-1 NaCl). Two metabolic inhibitors of ethanol metabolism were also used namely 4-methylpyrazole (alcohol dehydrogenase inhibitor) and cyanamide (acetaldehyde dehydrogenase inhibitor) which in ethanol-dosed rats have been shown to either decrease or increase acetaldehyde formation, respectively. After 2.5 h, fractional rates of protein synthesis (i.e. the percentage of tissue protein renewed each day) were measured with a large (i.e. 'flooding') dose of L-[4-3H]phenylalanine (150 mumol (100 g)-1 body weight into a lateral vein). This dose of phenylalanine effectively floods all endogenous free amino acid pools so that the specific radioactivity of the free amino acid at the site of protein synthesis (i.e. the amino acyl tRNA) is reflected by the specific radioactivity of the free amino acid in acid-soluble portions of cardiac homogenates. The results showed that ethanol alone and ethanol plus 4-methylpyrazole decreased the fractional rates of mixed, myofibrillar (contractile) and sarcoplasmic (non-contractile) protein synthesis to the same extent (by approx. 25 per cent). Profound inhibition (i.e. 80 per cent) in the fractional rates of mixed, myofibrillar and sarcoplasmic protein synthesis occurred when cyanamide was used to increase acetaldehyde formation. There was also a significant decrease in cardiac DNA content. The results suggest that acute ethanol-induced cardiac injury in the rat may be mediated by both acetaldehyde and ethanol.
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PMID:Ethanol-induced inhibition of ventricular protein synthesis in vivo and the possible role of acetaldehyde. 845 36

The sequence has been determined of 68 897 bp of genomic DNA including the expressed mat1 mating-type locus from Schizosaccharomyces pombe h(-S) strain 972. The DNA sequence, located on the long arm of fission yeast chromosome II and contained in two cosmid clones, was analysed to reveal one autonomously replicating sequence, two retrotransposon long terminal repeats (LTRs), one tRNA(Gly) gene and 33 open reading frames (ORFs), of which 15 contain introns. Nine of these ORFs code for previously described genes (trt1, rpl10, rps21, nif1, sui1 (psu1), matMi, matMc, let1 and rpa4), one of which (trt1) contains 15 introns, the highest number yet recorded in a gene of S. pombe. Of the remaining 24 ORFs, sequence similarity suggests that the function of 13 of the encoded proteins may be predicted and these include four mitochondrial proteins, two transport proteins, two signalling molecules, a component of serine palmitolytransferase, a homologue of 3-methyladenine DNA glycosylase, a multifunctional alcohol dehydrogenase, a killer toxin sensitivity factor and an acetyl transferase. Six deduced sequences appear to be related to proteins of unknown function in Saccharomyces cerevisiae or S. pombe and the remaining five are hypothetical proteins.
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PMID:The mating-type region of Schizosaccharomyces pombe h(-S) 972: sequencing and analysis of 69 kb including the expressed mat1 locus. 1092 28

The evolution of codon bias, the unequal usage of synonymous codons, is thought to be due to natural selection for the use of preferred codons that match the most abundant species of isoaccepting tRNA, resulting in increased translational efficiency and accuracy. We examined this hypothesis by introducing 1, 6, and 10 unpreferred codons into the Drosophila alcohol dehydrogenase gene (Adh). We observed a significant decrease in ADH protein production with number of unpreferred codons, confirming the importance of natural selection as a mechanism leading to codon bias. We then used this empirical relationship to estimate the selection coefficient (s) against unpreferred synonymous mutations and found the value (s >or= 10(-5)) to be approximately one order of magnitude greater than previous estimates from population genetics theory. The observed differences in protein production appear to be too large to be consistent with current estimates of the strength of selection on synonymous sites in D. melanogaster.
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PMID:In vivo introduction of unpreferred synonymous codons into the Drosophila Adh gene results in reduced levels of ADH protein. 1258 11


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