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

---

Query: EC:2.6.1.44 (AGT)
770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mutation of the psbA gene was identified in photoautotrophic potato (Solanum tuberosum L. cv Superior x U.S. Department of Agriculture line 66-142) cells selected for resistance to 6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine (atrazine). Photoaffinity labeling with 6-azido-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine detected a thylakoid membrane protein with a M(r) of 32,000 in susceptible, but not in resistant, cells. This protein was identified as the secondary quinone acceptor of photosystem II (QB) protein. Atrazine resistance in selected cells was attributable to a mutation from AGT (serine) to ACT (threonine) in codon 264 of the psbA gene that encodes the QB protein. Although the mutant cells exhibited extreme levels of resistance to atrazine, no concomitant reductions in photosynthetic electron transport or cell growth rates compared to the unselected cells were detected. This is in contrast with the losses in productivity observed in atrazine-resistant mutants that contain a glycine-264 alteration.
...
PMID:A serine-to-threonine substitution in the triazine herbicide-binding protein in potato cells results in atrazine resistance without impairing productivity. 802 41

The effect of human O6-methylguanine-DNA methyltransferase (MGMT) on the cytotoxicity, the mutagenicity, and the specific kinds of base substitutions induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were examined in non-MGMT transfected Chinese hamster ovary cells (CHOM cells) and in those cells which had been transfected with human MGMT complementary DNA (AGT cells). AGT cells containing a high level of human MGMT activity were markedly more resistant to the cytotoxic and mutagenic effects of MNNG than CHOM cells which had no detectable MGMT activity. The dosages of MNNG which reduced to 50% of colony forming ability were estimated to be 0.8 microM for CHOM and 10 microM for AGT cells. The induction frequency of 6-thioguanine-resistant cells was significantly declined in AGT cells. At 4 microM MNNG, this frequency was declined from 273 mutants/10(6) viable CHOM cells to 13 mutants/10(6) viable AGT cells. The entire coding region of the hypoxanthine (guanine) phosphoribosyltransferase (hprt) gene in 37 AGT and 22 CHOM mutants was characterized by direct sequencing of the mRNA-polymerase chain reaction-amplified complementary DNA. Base changes at the intron-exon boundaries of the hprt DNA in the splicing mutants were further examined. Those results indicated that G to A transitions were significantly reduced in MNNG-treated AGT cells (chi 2 test, P < 0.001), suggesting that O6-methylguanine was repaired error free by human MGMT. In contrast, no difference arose in the frequencies of T to C transitions induced by MNNG in these two populations. All of the G to A transitions induced in AGT cells were located on the nontranscribed strand, assuming that the causative lesion was O6-methylguanine (P < 0.05). Such a strand specificity was not observed in CHOM mutants. Most of the G to A transitions observed in CHOM mutants were located at the middle guanine of 5'-GGPu sequences. Transitions observed at these sites, particularly 5'-GGG, were significantly reduced in AGT mutants (P < 0.05). Our results have suggested that human MGMT specifically repairs O6-methylguanine with a preference to remove those located on the transcribed strand and middle guanine of 5'-GGG.
...
PMID:Strand- and sequence-specific attenuation of N-methyl-N'-nitro-N-nitrosoguanidine-induced G.C to A.T transitions by expression of human 6-methylguanine-DNA methyltransferase in Chinese hamster ovary cells. 803 7

Oxidants are suspected to represent important human carcinogens. They are mutagenic and may participate in the activation of proto-oncogenes and the inactivation of tumor suppressor genes. We have studied the capacity of hydrogen peroxide plus ferric chloride (FeCl3) to induce base pair changes in the hotspot codons 248 and 249 of the p53 tumor suppressor gene in human fibroblasts. In codon 248 (CGG) H2O2/FeCl3 only induced the transversion of G to C in the second position and the transition of G to A in the third position. No evidence was obtained for spontaneous or oxidant-induced deamination of 5-methylcytosine in the CpG dinucleotide of codon 248 since neither C to T transitions in the first position nor G to A transitions in the middle position were observed. H2O2/FeCl3 efficiently induced G to T transversions at both G-residues of codon 249 (AGG) and C to A transversions at the first position of codon 250 (CCC). It is evident that H2O2/FeCl3 possesses essentially the same mutagenic specificity for codons 249 and 250 of p53 as bulky carcinogens such as aflatoxin B1, benzo(a)pyrene or heterocyclic amines. In particular, it is not possible to eliminate oxidants from the list of candidate carcinogens which may be responsible for the high incidence of p53 codon 249 AGT mutations in hepatocellular carcinoma from certain areas of the world.
...
PMID:Oxy-radical induced mutagenesis of hotspot codons 248 and 249 of the human p53 gene. 803 11

Cerulenin, an antifungal antibiotic produced by Cephalosporium caerulens, is a potent inhibitor of fatty acid synthase in various organisms, including Saccharomyces cerevisiae. The antibiotic inhibits the enzyme by binding covalently to the active center cysteine of the condensing enzyme domain. We isolated 12 cerulenin-resistant mutants of S. cerevisiae following treatment with ethyl methanesulfonate. The mechanism of cerulenin resistance in one of the mutants, KNCR-1, was studied. Growth of the mutant was over 20 times more resistant to cerulenin than that of the wild-type strain. Tetrad analysis suggested that all mutants mapped at the same locus, FAS2, the gene encoding the alpha subunit of the fatty acid synthase. The isolated fatty acid synthase, purified from the mutant KNCR-1, was highly resistant to cerulenin. The cerulenin concentration causing 50% inhibition (IC50) of the enzyme activity was measured to be 400 microM, whereas the IC50 value was 15 microM for the enzyme isolated from the wild-type strain, indicating a 30-fold increase in resistance to cerulenin. The FAS2 gene was cloned from the mutant. Sequence replacement experiments suggested that an 0.8 kb EcoRV-HindIII fragment closely correlated with cerulenin resistance. Sequence analysis of this region revealed that the GGT codon encoding Gly-1257 of the FAS2 gene was altered to AGT in the mutant, resulting in the codon for Ser. Furthermore, a recombinant FAS2 gene, in which the 0.8 Kb EcoRV-HindIII fragment of the wild-type FAS2 gene was replaced with the same region from the mutant, when introduced into FAS2-defective S. cerevisiae complemented the FAS2 phenotype and showed cerulenin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Cerulenin-resistant mutants of Saccharomyces cerevisiae with an altered fatty acid synthase gene. 804 67

Mutations in the p53 tumor suppressor gene are detected in approximately half of non-melanoma skin cancers. The type of base-pair changes observed strongly suggests solar radiation as the causative mutagen. Mutations are distributed nonrandomly and form moderate hotspots. We studied the capacity of ultraviolet B light (UVB, 280-320 nm) to induce base-pair changes into the p53 exon 7 sequence extending from nt 14067 to 14075 in human skin fibroblasts. This sequence contains hotspot codon 248. UVB induced mostly C-->A and G-->T transversions. The base-pair change with the highest relative abundance was C-->A in the first position of codon 250 (CCC-->ACC), followed by (in diminishing relative abundance) G-->T in the third position of codon 249 (AGG-->AGT), C-->A in the first position of codon 248 (CGG-->AGG), and C-->A in the third position of codon 247 (AAC-->AAA). The C-->T transition in the third position of codon 247 (AAC-->AAT) occurred with moderate efficiency. These base-pair changes are compatible with pyrimidine photodimers as premutagenic lesions, but they could also form opposite 8-hydroxyguanine, which is the major oxidation product of guanine. No evidence was obtained for the presence of tandem double CC-->TT transitions in the untranscribed strand at codons 247/248 and 250. The relative abundance of mutations induced by UVB in the p53 sequence extending from codon 247 to 250 in human fibroblasts does not correlate with mutations observed in the DNA from non-melanoma skin cancer. This lack of correlation suggests that the mutability of this p53 sequence at the DNA level plays only a minor role in the pathogenesis of non-melanoma skin cancer in humans.
...
PMID:Ultraviolet B light-induced mutagenesis of p53 hotspot codons 248 and 249 in human skin fibroblasts. 806 78

We have evidence that the limulus (Tachypleus tri-dentatus) hemocyte transglutaminase (TGase) has a molecular mass of 86 kDa and properties of the mammalian type II TGase-like enzyme (Tokunaga, F., Yamada, M., Miyata, T., Ding, Y.-L., Hiranaga-Kawabata, M., Muta, T., Iwanaga, S., Ichinose, A., and Davie, E.W. (1993) J. Biol. Chem. 268, 252-261). We present here the cDNA and amino acid sequences, and localization of the TGase in various tissues of limulus. The cloned cDNA for TGase consists of 2,884 base pairs. An open reading frame of 2,292 base pairs encodes a sequence comprising 764 residues of the mature protein with molecular masses of 87,021 and 87,110 Da, due to two different clones. The discrepancies of nucleotides in these two clones result in 3 amino acid exchanges at positions Gly452(GGT)-Arg(CGT), Ser477(AGT)-Cys(TGT), and Ile486(ATC)-Ser(AGC), respectively. Northern blot analysis on a total RNA extracted from various tissues of limulus revealed that TGase is expressed with 3.0 kilobases of a single type of mRNA, mainly in hemocytes, hepatopancreas, and gastric tissues. Limulus TGase shows significant sequence similarity with the mammalian TGase family, as follows: guinea pig liver TGase (32.7%), human factor XIIIa subunit (34.7%), human keratinocyte TGase (37.6%), and human erythrocyte band 4.2 (23.0%). Limulus TGase has a unique NH2-terminal cationic extension of 60 residues with no homology to the NH2 termini of mammalian TGases. Based on the alignment of the amino acid sequence of limulus TGase with those of the known TGase family, a phylogenetic tree representing an evolutionary relationship among the family members was inferred by the neighbor joining method.
...
PMID:Limulus hemocyte transglutaminase. cDNA cloning, amino acid sequence, and tissue localization. 809 43

To examine the significance of mutation of the p53 tumour suppressor gene in the development of human hepatocellular carcinoma in a high-prevalence area for hepatitis B viral infection but a low-exposure area for aflatoxin B1, the spectrum of p53 gene mutations was examined in 21 tumour samples from Hong Kong Chinese patients, all of whom were HBsAg positive. DNA sequencing covering exons 5 to 9 of the p53 gene and Hae III restriction enzyme digestion for preliminary assessment of mutation at codon 249 were performed. Immunohistochemical staining with anti-p53 monoclonal antibodies was done on both tumour and nontumour liver tissues. Six tumours (28.6%) showed a p53 mutation and all were point mutations. Of the six point mutations, two (9.5%) were at codon 249 and both were G to T transversions (AGG-->ATG and AGG-->AGT transversions). The remaining point mutations were transversions scattered at codon 172 (exon 5), 214 (exon 6), 273 (exon 8) and 330 (exon 9). Mutated p53 protein was detected in five of these six cases with demonstrable point mutations by DNA sequencing, in contrast to none detected in all of the 15 cases without demonstrable point mutations. The presence of p53 mutations, including those at codon 249, did not show a significant association with tumour size, sex, age, tumour invasiveness in terms of liver invasion, microsatellites and venous permeation, cirrhosis and encapsulation, but tumours with low cellular differentiation tended to have a higher incidence (71%) of point mutations than those with high cellular differentiation (8%). In conclusion, both the overall p53 mutation rate and that a codon 249 in HCC in Hong Kong Chinese are lower than those reported in tumours from China and sub-Saharan Africa. The low mutation rate at codon 249 is compatible with a low aflatoxin exposure. A special type of p53 mutation has not been found to be associated with hepatitis B viral infection. Mutations of p53 gene tends to occur in tumours with low cellular differentiation, suggesting a late occurrence in the event of tumour progression.
...
PMID:p53 gene mutation spectrum in hepatocellular carcinomas in Hong Kong Chinese. 810 45

The effects of glucagon on serine: pyruvate/alanine: glyoxylate aminotransferase (SPT/AGT) gene expression were studied in primary cultured rat hepatocytes. When hepatocytes had been precultured for 16-18 h under serum- and hormone-free conditions, the addition of glucagon caused (after a lag period of about 2 h) a remarkable increase in the cellular level of SPT/AGT mRNA by 4 h in a time- and dose-dependent manner. The induced mRNA was that for mitochondrial SPT/AGT, as judged by ribonuclease protection analysis. A nuclear run-on assay revealed that activation of transcription is responsible for the increase in mitochondrial SPT/AGT mRNA and that the maximal rate of transcription occurs 1.5 h after glucagon addition. The effect of glucagon was mimicked by 8-bromo-cAMP and suppressed by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide, an inhibitor of cAMP-dependent protein kinase (protein kinase A), while both 12-O-tetradecanoylphorbol-13-acetate and A23187 were without effect in elevating the SPT/AGT mRNA level, suggesting that the cAMP/protein kinase A system is involved in the regulation of SPT/AGT gene expression. In hepatocytes precultured for 16-18 h under serum- and hormone-free conditions, the glucagon-induced transcription was severely inhibited by cycloheximide. When the preculture was for 2 h, on the other hand, the activation of transcription by glucagon was more rapid, and the inhibition by cycloheximide was less than that observed with cells precultured for 16-18 h, suggesting that a short-lived protein factor is involved in the hormonal regulation. The glucagon-induced expression of the SPT/AGT gene was also turned off by dexamethasone.
...
PMID:Regulation by glucagon of serine: pyruvate/alanine: glyoxylate aminotransferase gene expression in cultured rat hepatocytes. 813 20

Zinc, a component of a large number of enzymes and an abundant and essential trace metal, alters the structure of AGCT sites in negatively supercoiled DNA. Related sequences show little or no effect. Cobalt and cadmium show reactivities similar to zinc. The conformational change in DNA was fine mapped with haloacetaldehydes using chemical cleavage or primer extension methods. Since a many fold excess of zinc to AGCT sites is required to saturate the reaction, we propose that the zinc-AGT complex is preferentially accessible to the haloacetaldehyde probes due to a conformational deformation. Hence, zinc is the smallest ligand (by approximately 500-fold) that causes a perturbation of a specific DNA sequence.
...
PMID:Zinc destabilizes DNA Watson-Crick pairs at AGCT. 814 38

The effect of nucleotide sequence on the binding of 7(R),8(S)-dihydroxy-9(S),10(R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] to the exocyclic amino group of deoxyguanosine was investigated in duplexes formed by self-complementary oligodeoxyribonucleotide decamers which contained two deoxyguanosines (dGs) within unique sequences. A 35S-postlabeling procedure was developed for analysis of (+)-anti-BPDE adducts as dinucleotides containing 5'-(+)-anti-BPDE-dG adducts. This allows identification of the 3' neighbor of the reacted guanine and permits quantitation of the binding of (+)-anti-BPDE to each specific guanine in the oligodeoxyribonucleotide duplexes. Of all the central dG-containing sequences studied, dG surrounded by deoxycytidines (CGC) reacted to the greatest extent: over 4-fold more (+)-anti-BPDE bound to this central dG compared to the least reactive deoxyguanosine (AGT). (+)-anti-BPDE exhibited a preference for binding to a central deoxyguanosine when either the 5' or 3' neighbor was deoxyguanosine. The binding of (+)-anti-BPDE to oligodeoxyribonucleotide duplexes containing different numbers of consecutive dGs was analyzed in order to determine how the length of these sequences influences binding. Increases in the length of consecutive deoxyguanosine residues from 3 to 5 had little effect on the quantity of (+)-anti-BPDE bound to dG above that expected from the presence of a neighboring dG and an increase in the number of dG residues available for reaction. The results obtained with these oligodeoxyribonucleotide duplexes were consistent with the data available for the reaction of (+)-anti-BPDE with DNA, indicating that these duplexes are a valuable model for studying the effect of base sequence on the interaction of BPDE isomers with DNA. The dinucleotide postlabeling technique developed for these studies, with appropriate oligodeoxyribonucleotides and chromatographic conditions, will be useful for determining the effect of base sequence on the binding of other hydrocarbon diol epoxides as well as other reactive hydrocarbon metabolites to deoxyguanosine or deoxyadenosine in oligodeoxyribonucleotide duplexes and fragments of DNA.
...
PMID:Base sequence selectivity in the binding of 7(R),8(S)-dihydroxy-9(S),10(R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene to oligodeoxyribonucleotide duplexes. 815 22


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

---