Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
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Previous results from this laboratory indicated that, in Escherichia coli K12, a new class of missense suppressors, which read the lysine codons AAA and AAG, may be misacylated lysine transfer RNAs. We therefore isolated and determined the nucleotide sequence of the lysine tRNA from two of the suppressor strains. In each case, we found both wild-type and mutant species of lysine tRNA, a result consistent with evidence that there are two genes for lysine tRNA in the E coli genome. The wild-type sequence was essentially identical to that reported for lysine tRNA from E. coli B. The mutant species isolated from each suppressor strain had a U for C70 nucleotide substitution, demonstrating that the AAG suppressor is a mutant lysine tRNA. The nucleotide substitution in the amino acid acceptor stem is consistent with the in vivo evidence that the suppressor corrects AAA and AAG missense mutations by inserting an amino acid other than lysine during polypeptide synthesis. This report represents the first verification of missense suppression caused by misacylation of a mutant tRNA.
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PMID:Nucleotide substitution in the amino acid acceptor stem of lysine transfer RNA causes missense suppression. 636 14

After our first observation of codon context effects in missense suppression ( Murgola & Pagel , 1983), we measured the suppression of missense mutations at two positions in trpA in Escherichia coli. The suppressible codons in the trpA messenger RNA were the lysine codons, AAA and AAG, and the glutamic acid codons, GAA and GAG. The mRNA sites of the codons correspond to amino acids 211 and 234 of the trpA polypeptide, positions at which glycine is the wild-type amino acid. Our data demonstrated codon context effects with both pairs of codons. The results indicate that suppression of AAA and AAG by mutant lysine transfer RNAs was more efficient at 211 than at 234, whereas suppression of GAA and GAG by two different mutant glycine tRNAs was more efficient at 234 than at 211. In general, the context effects were more pronounced with GAG and AAG than with GAA and AAA. (In some instances it appeared that suppression of GAA or AAA at a given position was more effective than suppression of GAG or AAG.) By contrast, no context effects were observed with a glyT suppressor of AAA and AAG, a glyT GAA/G-suppressor, and a glyU suppressor of GAG. Our observation of this phenomenon in missense suppression demonstrates that codon context can affect polypeptide elongation and that the effects can be different depending on the codons and tRNAs examined. It is suggested that tRNA-tRNA interaction on the ribosome is involved in the observed context effects.
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PMID:Codon context effects in missense suppression. 637 55

We have sequenced a lysine tRNA from mosquito mitochondria that has the anticodon CUU. The preponderance of AAA lysine codons in insect mitochondrial genes, the parsimonious organization of the genomes, and the fact that this tRNA is a major component of the mosquito mitochondrial tRNA complement, lead us to suggest that the CUU anticodon recognizes AAC and AAA codons.
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PMID:A major lysine tRNA with a CUU anticodon in insect mitochondria. 656 19

The reading of glutamine and lysine codons during protein synthesis in vitro has been investigated using an MS2-RNA-programed system derived from Escherichia coli. Under conditions when either glutaminyl-tRNA1Gln (s2UUG) or glutaminyl-tRNA2Gln (CUG) was the only source of glutamine for protein synthesis both tRNAs were able to read the glutamine codons CAA and CAG as indicated by the incorporation of labeled glutamine into the pertinent coat protein tryptic peptides. On the other hand, when the two glutamine tRNAs competed for the codon CAA the reading efficiency of the anticodon s2UUG, which reads the codon according to the wobble rules, was almost 40 times higher than that of the competing anticodon CUG, which reads the codon by "two out of three," i.e. it cannot form a regular base pair with the third codon position. In reading the codon CAG the anticodon CUG was approximately eight times more efficient than the anticodon s2UUG. The lysyl-tRNA1Lys (CUU) could not alone sustain any detectable coat protein synthesis in the MS2 system indicating that there was no significant reading of the lysine codon AAA. This conclusion is supported by the outcome of experiments where lysyl-tRNA1Lys (CUU) and lysyl-tRNA2Lys (s2UUU) competed for the codon AAA. The reading efficiency of the anticodon CUU was less than 1% of that of the competing s2UUU which represents the limit of resolution of our experimental system. When the two lysine tRNAs competed for the codon AAG the anticodon CUU was about four times more efficient than s2UUU. These results are discussed in the context of the two out of three hypothesis, which attempts to relate the frequency of such reading to the hydrogen bonding properties of the codon nucleotides.
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PMID:Codon reading and translational error. Reading of the glutamine and lysine codons during protein synthesis in vitro. 678 93

Isoacceptors of rabbit liver tRNALys which preferentially translate the codon AAG were compared for their function in several aspects of translation. As shown in other laboratories, Lys-tRNALys1,2 are two isoacceptors which differ from each other by a single base pair and are fully modified with N6-threonyl-adenosine adjacent to the anticodon. Lys-tRNALys4, which occurs commonly in rapidly dividing mammalian cells and tissues, is hypomodified at several bases and contains a precursor of N6-threonyl-adenosine next to its anticodon. These isoacceptors were incubated in cell-free protein synthesizing systems which contain rabbit globin mRNA. (Lys-tRNALys3 which translates AAA was also included.) The resulting globin was isolated and digested with trypsin, and the relative incorporation of lysine from Lys-tRNALys1,2 and from Lys-tRNALys4 into lysine-containing sites in the globin peptides as determined. Lys-tRNALys1,2 and Lys-tRNALys4 translate AAG preferentially, but Lys-tRNALys4 wobbles more than the former and translates AAA codons more efficiently. Overall, Lys-tRNALys1,2 is preferred in globin synthesis by about 30% compared to Lys-tRNALys4, and with one exception, the incorporation of lysine into the individual AAG lysine-containing sites in globin occurs more efficiently from Lys-tRNALys1,2. There is, however, considerable variation from site to site in the relative efficiencies of the Lys-tRNAs in incorporation.
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PMID:The effects of a post-transcriptional modification on the function of tRNALys isoaccepting species in translation. 691 45

A unique phosphoprotein, which contains an uncommon amino acid, alpha-amino adipic acid (alpha-AAA), was isolated from unerupted bovine teeth by extensive EDTA demineralization. The alpha-AAA in the protein hydrolysates was identified based on the elution time on an amino acid analyzer using the sodium and lithium citrate buffer in a dual column system, and its identity was confirmed by comparisons of its DNS derivative with that of authentic alpha-AAA. This result suggests that the lysine residues in the phosphoprotein may be deaminated by an amine oxidase into allysine and further oxidized to alpha-AAA.
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PMID:Identification and quantification of alpha-amino adipic acid in bovine dentine phosphoprotein. 741 98

We generated variants of the human immunodeficiency virus type 1 (HIV-1) that are resistant to 2',3'-dideoxycytidine (ddC) and 2',3'-didehydro-3'-deoxythymidine (d4T) by in vitro selection in MT-4 cells. Portions of flanking protease and integrase sequences as well as the complete reverse transcriptase (RT) open-reading frame of these viruses were cloned and sequenced, using polymerase chain reaction (PCR)-based methods. Mutations were observed at amino acid position 65 (Lys-->Arg; AAA-->AGA) when ddC was employed in the selection procedure and at site 50 (Ile-->Thr; ATT-->ACT) when d4T was used. We confirmed the ability of these mutations to confer diminished sensitivity for these compounds by site-directed mutagenesis, in which these mutations were inserted into the pol gene of infectious recombinant HXB2-D DNA. Viruses that contained the site 65 mutation possessed approximately 5-10 fold resistance against ddC when compared with wild-type HXB2-D. The site 50 mutation conferred approximately 30-fold resistance to d4T in these same assays. Similar results were obtained using primary cord blood lymphocytes in drug resistance assays, indicating that these mutations could confer drug resistance in more than one cell type and that the respective mutations could be expressed in cells of primary origin. No cross-resistance against 3'-azido-3'-deoxythymidine (AZT) was noted for either the site 65 or 50 mutations.
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PMID:Identification of novel mutations that confer drug resistance in the human immunodeficiency virus polymerase gene. 751 78

The technique of in vitro selection was used to generate variants of the human immunodeficiency virus type 1 that are resistant to 2',3'-dideoxycytidine (ddC). Most of the pol regions of such viruses, including the complete reverse transcriptase open reading frame and portions of flanking protease and integrase genes, were cloned and sequenced, using PCR-based procedures. Mutations were variously detected at amino acid site 65 (Lys-->Arg; AAA-->AGA) and at a previously reported codon, site 184 (Met-->Val; ATG-->GTG). We introduced the site 65 mutation into the pol gene of infectious, cloned HxB2-D DNA by site-directed mutagenesis in order to confirm by viral replication assay the importance of this site in conferring resistance to ddC. The recombinant virus possessed greater than 10-fold resistance against this compound in comparison with parental HxB2-D. Cross-resistance of approximately 20- and 3-fold, respectively, was detectable against the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine and 2',3'-dideoxyinosine but not against 3'-azido-3'-deoxythymidine. Combinations of the site 65 and 184 mutations did not yield levels of resistance higher than those attained with the site 65 mutation alone. The presence of the site 65 mutation was confirmed by PCR analysis of peripheral blood mononuclear cells from patients on long-term ddC therapy in 4 of 11 cases tested. Viruses that possessed a ddC resistance phenotype were isolated from subjects whose viruses contained the site 65 mutation in each of four instances. Four of these clinical samples were also demonstrated to possess the Met-184-->Val mutation, and one of them possessed both the Lys-65-->Arg and Met-184-->Val substitutions. Direct cloning and sequencing revealed the site 65 mutation in viruses isolated from these individuals.
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PMID:Identification of a mutation at codon 65 in the IKKK motif of reverse transcriptase that encodes human immunodeficiency virus resistance to 2',3'-dideoxycytidine and 2',3'-dideoxy-3'-thiacytidine. 751 55

The existence of Helicobacter pylori in the biliary tract was investigated. Seven bile samples were included in this study. Among them, six bile samples were collected by percutaneous transhepatic cholangiodrainage and the other by needle aspiration during cholecystectomy. Using nested PCR with two sets of primers homologous to the urease A gene, Helicobacter pylori DNA was detected. Three samples, one from a patient with advanced gastric cancer involving the pancreatic head and two from patients with pancreatic head tumor, were found to be positive for Helicobacter pylori DNA. On the other hand, three samples from patients with cholangiocarcinoma and one from a patient with chronic cholecystitis were all negative. To further verify the specificity of our PCR analysis, partial sequences of the PCR products from the three positive samples were analyzed by direct sequencing. Several silent mutations and a missense mutation (AAA to AGA; Lys-164 to Arg-164) were identified in the urease A gene. We conclude that Helicobacter pylori DNA can be easily detected in the bile samples. The possibility of asymptomatic cholangitis caused by this organism requires further investigation.
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PMID:Detection and partial sequence analysis of Helicobacter pylori DNA in the bile samples. 758 92

Maackia amurensis haemagglutinin (MAH) is a leguminous lectin which preferentially binds to a cluster of sialylated O-linked carbohydrate chains (Konami Y, Yamamoto K. Osawa T, Irimura T (1994) FEBS Lett 342:334-38). In the present study a 950 bp cDNA clone encoding MAH was isolated from a cDNA library constructed from germinated Maackia amurensis seeds. From the nucleotide sequence, MAH was predicted to consist of 285 amino acid residues containing a signal peptide of 29 amino acids. The results also confirmed our previous findings from the amino acid sequence analysis, which indicated that two highly conserved amino acid residues in all other well-known leguminous lectins were replaced in MAH. These residues were lysine-105 and aspartic acid-135. The corresponding amino acid residues in other leguminous lectins were glycine and asparagine, respectively. These differences were due to the presence of nucleotides AAA and GAT in place of AAT/C and GGA/T.
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PMID:Cloning and sequence analysis of the Maackia amurensis haemagglutinin cDNA. 769 60


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