Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The amino acid substitutions responsible for the temperature-sensitive (ts) and mutator phenotypes of the classical bacteriophage T4 DNA polymerase mutant tsL56 were determined. tsL56 DNA polymerase has two mutations in the 5' end of the DNA polymerase gene (g43) that produce two amino acid substitutions: codon 89, alanine to threonine, and codon 363, aspartate to asparagine. Both mutations are required for the strong ts and mutator phenotypes. The increased error rate of the tsL56 DNA polymerase is due to a reduction in 3'----5' exonuclease activity relative to polymerase activity (N. Muzyczka, R. L. Poland, and M. J. Bessman, J. Biol. Chem. 247:7116-7122, 1972). Thus, the locations of the tsL56 mutations suggest that the 3'----5' exonuclease domain resides in the N-terminal region. Several other ts DNA polymerase mutant strains isolated with tsL56 also have mutator or antimutator phenotypes. The nucleotide changes in these important mutant strains were also determined. This mutant collection, combined with collections of g43 amber mutants and mutants selected on the basis of a strong mutator phenotype (L. J. Reha-Krantz, J. Mol. Biol. 202:711-724, 1988), contains nearly 70 different DNA polymerase mutations. The numerous T4 DNA polymerase mutations are valuable for DNA polymerase structure-function and fidelity studies.
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PMID:Locations of amino acid substitutions in bacteriophage T4 tsL56 DNA polymerase predict an N-terminal exonuclease domain. 267 3

mtDNA of the hybridogenetic hybrid frog Rana esculenta from Switzerland, Austria, and Poland was compared to mtDNA of the parental species R. ridibunda and R. lessonae using electrophoretic analysis of restriction enzyme fragments. Two mtDNA phenotypes, with 3.4% sequence divergence, are present in R. lessonae: type C is found in Poland, and type D is found in Switzerland. Rana ridibunda from Poland has either of two mtDNA phenotypes: type A is the typical ridibunda mtDNA, and type B is a lessonae mitochondrial genome, introgressed into R. ridibunda, that differs from type C mtDNA of R. lessonae by only 0.3%. Each of the three lessonae genomes differs from A, the typical ridibunda mtDNA, by approximately 8%. All four types of mtDNA (A and B of R. ridibunda, C and D of R. lessonae) are found in R. esculenta. Of 62 R. esculenta from Poland, 58 had type C, three had type A, and one had type B mtDNA. All nine R. esculenta from Switzerland had type D mtDNA. All three R. esculenta from Austria, from a population in which males of R. esculenta are rare, had ridibunda mtDNA, two having type B and one having type A. Both field observations and studies of mating preference indicate that the primary hybridizations that produce R. esculenta are between R. ridibunda females and R. lessonae males; thereafter, R. esculenta lineages are usually maintained by matings of R. esculenta females with R. lessonae males. The presence of ridibunda mtDNA in the three R. esculenta sampled from Austria, its occasional presence in R. esculenta populations in Poland, and its absence from R. esculenta in Switzerland support both the direction of the original hybridization and the rarity of formation of new R. esculenta lineages. The preponderance of R. esculenta individuals with lessonae mtDNA in our samples from central Europe suggests that most lineages have gone through at least one mating between an R. lessonae female and an R. esculenta male. This reveals a greater reproductive role for R. esculenta males than their partial sterility and infrequent matings would suggest.
Mol Biol Evol 1986 Jan
PMID:Evolutionary history of the hybridogenetic hybrid frog Rana esculenta as deduced from mtDNA analyses. 283 87

The presence of virus-derived RNA was investigated in 38 axenically growing Giardia isolates from different geographic areas. The RNA virus was demonstrated in Giardia strains from humans in the U.S.A., England and the majority of strains from Poland. Two strains isolated respectively from a cat and a cavia also contained it. Giardia strains from humans in Belgium and Israel did not contain this RNA virus. Transfection of the RNA virus was accomplished from English and Polish strains, as well as from the cat isolate to isolates lacking it. Differences were observed both in sensitivity of Giardia strains to transfection and in infectivity of the RNA virus from different Giardia strains. Transfection could be carried out with sonicated Giardia extract as well as with filter sterilized medium in which Giardia strains containing RNA virus had grown. The RNA virus did not replicate in Giardia-free medium. No correlation could be demonstrated between the presence of the RNA virus in Giardia isolates and their in vitro resistance to some antiprotozoal drugs, nor with the fact that the strain originated from symptomatic or asymptomatic carriers. The presence of the RNA virus in Giardia trophozoites did not influence the isoenzyme patterns or restriction endonuclease patterns of repetitive DNA. A correlation may exist with the length of time since the isolation in axenic culture of the strain.
Mol Biochem Parasitol 1987 Feb
PMID:Occurrence and transfection of a Giardia virus. 357 50

The stability parameters delta Gst, delta Hst and delta Sst of native basic pancreatic trypsin inhibitor (BPTI) have been characterized by microcalorimetric unfolding studies in various buffer solutions, at different pH values and in the presence of guanidine hydrochloride. The unfolding enthalpy of BPTI, in contrast ot other globular proteins, exhibits a very small dependence on temperature, which results in a characteristic different temperature dependence of the Gibbs energy of stabilization. BPTI has a very high specific Gibbs energy of stabilization, which renders the slow exchange rates of amide protons understandable. Comparison of the unfolding entropy of BPTI at 110 degrees C with corresponding values of other proteins, revealed that the delta S values of BPTI are lower by 2.9 J/(K X residue). This lower value of the unfolding entropy is in good agreement with predictions of a theoretical study by Poland & Scheraga (1965) where the influence of crosslinks on the configurational entropy has been studied. Additionally, we were able to calculate an interaction enthalpy per site of -5.6 kJ/mol based on the measurements of unfolding of BPTI in 6 M-guanidine hydrochloride.
J Mol Biol 1983 Nov 05
PMID:Basic pancreatic trypsin inhibitor has unusual thermodynamic stability parameters. 619 47

Cecidophyopsis mites were studied by PCR amplification of parts of their ribosomal DNA, followed by restriction enzyme analysis. Mite specimens on Ribes nigrum (black currant) from six countries gave the same digestion pattern, which was distinct from the pattern for mites found on R. rubrum from Poland and Finland and for R. grossularia from the USA. This suggests that each Ribes species is host to a different mite species: C. ribis, C. selachodon and C. grossulariae, respectively. Two other mite samples from R. alpinum and R. aureum were identical but were distinct from each of the other species.
Mol Ecol 1995 Jun
PMID:Species identification of Cecidophyopsis mites (Acari: Eriophyidae) from different Ribes species and countries using molecular genetics. 766 55

We have investigated the effects of TCPOBOP (1,4-bis[2-(3,5- dichloropyridyloxy)]benzene), a potent cytochrome P-450-inducing agent [Poland, Mak, Glover, Boatman, Ebetino and Kende (1980) Mol. Pharmacol. 18, 571-580], on cytochrome P-450 isoenzyme expression in the mouse. Hepatic cytochrome P-450s from several distinct gene families were strikingly induced by a single dose of 75 micrograms of the compound. Northern-blot analysis demonstrated that this induction was almost certainly due to transcriptional activation of the cytochrome P-450 genes. The potency of this inductive effect was further reflected in the finding that cytochrome P-450 levels were still increased 12 weeks after a single injection of 75 micrograms of this compound. Interestingly, the mRNA levels of certain other genes, including those of metallothionein and the mouse major urinary proteins, were also induced. In view of the similarity in the effects of TCPOBOP and the synthetic glucocorticoid dexamethasone on mouse hepatic gene expression, we determined whether TCPOBOP acts through the glucocorticoid receptor. This did not, however, appear to be the case. Experiments with hypophysectomized animals demonstrated that TCPOBOP action was not regulated indirectly via the pituitary. In addition, induction of mouse Cyp2b protein by TCPOBOP in a primary culture of mouse hepatocytes suggests that the compound has a direct action on mouse liver. The above findings demonstrate that TCPOBOP is one of the most potent modulators of cytochrome P-450 gene expression described to date. It is not inconceivable that a single dose of this compound may alter hepatic gene expression for the majority of the lifespan of a mouse.
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PMID:1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene, an extremely potent modulator of mouse hepatic cytochrome P-450 gene expression. 843 79

Crystal structures of adenylosuccinate synthetase from Escherichia coli complexed with Mg2+, 6-thiophosphoryl-IMP, GDP, and hadacidin at 298 and 100 K have been refined to R-factors of 0.171 and 0.206 against data to 2.8 and 2.5 A resolution, respectively. Interactions of GDP, Mg2+ and hadacidin are similar to those observed for the same ligands in the complex of IMP, GDP, NO3-, Mg2+ and hadacidin (Poland, B. W., Fromm, H. J. & Honzatko, R. B. (1996). J. Mol. Biol. 264, 1013-1027). Although crystals were grown from solutions containing 6-mercapto-IMP and GTP, the electron density at the active site is consistent with 6-thiophosphoryl-IMP and GDP. Asp-13 and Gln-224 probably work in concert to stabilize the 6-thioanion of 6-mercapto-IMP, which in turn is the nucleophile in the displacement of GDP from the gamma-phosphate of GTP. Once formed, 6-thiophosphoryl-IMP is stable in the active site of the enzyme under the conditions of the structural investigation. The direct observation of 6-thiophosphoryl-IMP in the active site is consistent with the putative generation of 6-phosphoryl-IMP along the reaction pathway of the synthetase.
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PMID:Entrapment of 6-thiophosphoryl-IMP in the active site of crystalline adenylosuccinate synthetase from Escherichia coli. 918 42

The purpose of the present communication was to determine in lung cancer patients and healthy donors if there was a possible association between cancer and biomarkers of cytogenetic damage and ras p21 oncoprotein levels, and if various exogenous confounding factors (such as smoking habit) and endogenous ones (age, sex, etc.) could affect these biomarkers. Peripheral blood and plasma were collected from 31 lung cancer patients prior to treatment and 35 healthy donors of a similar socioeconomic status and from the same region in Poland. Chromosomal aberrations (CA), sister chromatid exchanges (SCE), high frequency cells (HFC), and proliferative rate index (PRI) were examined from the blood and ras p21 oncoproteins from the plasma. These parameters were used as biomarkers of genotoxic anomalies. All the biomarkers were examined for their relationship to confounding factors of age, sex, smoking habit, and immediate family cancer history. Results were analyzed by a t-test, analysis of variance (ANOVA), and stepwise multivariate regression analysis. All types of CA (including and excluding gaps), percent aberrant cells, SCE, and ras p21 oncoproteins were statistically significantly higher in cancer patients than in the healthy donors. Although there were smaller numbers of females in the cancer patients group who were older than the males, there was a difference due to sex (gender) with statistically significant increases in females for CA, SCE, and HFC, but there was no increase for ras p21 oncoproteins. Cytogenetic damage was not related to other cancers in the immediate families of the groups. All major CA parameters differed significantly between smokers and non-smokers in the cancer patients group, and SCE and HFC differed in the healthy donors group. Such parameters also showed a significant variability with the number of cigarettes smoked and the years of smoking habit. Multivariate regression analyses showed a significant association between cytogenetic damage, ras p21 oncoproteins, and cancer. In conclusion, cytogenetic damage and ras p21 oncoproteins in this study appear to be biomarkers associated with cancer, but have not been proved causally, and confounding factors such as age, sex (gender), and smoking can have an impact on them.
Environ Mol Mutagen 1997
PMID:Factors affecting various biomarkers in untreated lung cancer patients and healthy donors. 932 45

Adenylosuccinate synthetase from Escherichia coli is inactivated in a biphasic reaction by 6-(4-bromo-2,3-dioxobutyl)thioadenosine 5'-monophosphate (6-BDB-TAMP) at pH 7.0 and 25 degrees C. The initial fast-phase inactivation is not affected by the presence of active-site ligands and can be completely eliminated by blocking Cys291 of the enzyme with N-ethylmaleimide (NEM). Reaction of the NEM-treated enzyme with 6-BDB-[32P]TAMP results in 2 mol of reagent incorporated/mol of enzyme subunit. The inactivation kinetics of the slow-phase exhibit an apparent KI of 40.6 microM and kmax of 0.0228 min-1. Active-site ligands, either adenylosuccinate or IMP and GTP, completely prevent inactivation of the enzyme by 6-BDB-TAMP, whereas IMP or IMP and aspartate is much less effective in protection. 6-BDB-TAMP-inactivated enzyme has a 3-fold increase in Km for aspartate with no change in Km for IMP or GTP. Protease digestion of 6-BDB-[32P]TAMP inactivated enzyme reveals that both Arg131 and Arg303 are modified by the affinity-labeling reagent. The crystal structure [Poland, B. W., Fromm, H. J., and Honzatko, R. B. (1996) J. Mol. Biol. 264, 1013-1027] and site-directed mutagenesis [Kang, C., Sun, N., Poland, B. W., Gorrell, A., and Fromm, H. J. (1997) J. Biol. Chem. 272, 11881-11885] of E. coli adenylosuccinate synthetase show that Arg303 interacts with the carboxyl group of aspartate and the 2'-OH of the ribose of IMP and Arg131 is involved in stabilizing aspartate in the active site of the enzyme. We conclude that 6-BDB-TAMP functions as a reactive adenylosuccinate analogue in modifying both Arg131 and Arg303 in the active site of adenylosuccinate synthetase.
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PMID:Implication of arginine-131 and arginine-303 in the substrate site of adenylosuccinate synthetase of Escherichia coli by affinity labeling with 6-(4-bromo-2,3-dioxobutyl)thioadenosine 5'-monophosphate. 1023 26

In response to overfeeding, the Landes goose develops a fatty liver that is twice as large as that of the Poland goose, despite similar food intake. The role of hepatic lipogenesis in the genetic susceptibility to fatty liver was assessed in male overfed geese of the two breeds. For a similar hepatic protein content, total activities of malic enzyme, glucose-6-phosphate dehydrogenase, acetyl-Coa-carboxylase and fatty acid synthase, and specific activity and mRNA level of malic enzyme were about two-fold higher in the Landes goose. In the Poland goose, the weight of the fatty liver was correlated positively with the specific activity of ME and the VLDL concentration, which was not the case in the Landes breed. These results show that: (1) hepatic lipogenesis remains very active until the end of the overfeeding period; (2) the pentose-phosphate pathway may function in birds, contrary to what is assumed usually; (3) the level of hepatic lipogenesis is a major factor in the susceptibility to hepatic steatosis in different breeds of geese; and (4) ME activity may be a limiting factor of lipid synthesis in the less susceptible Poland breed.
Comp Biochem Physiol B Biochem Mol Biol 2000 May
PMID:Role of hepatic lipogenesis in the susceptibility to fatty liver in the goose (Anser anser). 1082 67


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