Global ETD Search

1	Studies on enzymes involved in the biosynthesis of pterin cofactors Baker, Stephen John January 1997 (has links) No description available. 547 Guanosine triphosphate cyclohydrolase I
2	Deoxyguanosine triphosphate, a possible target for reactive oxygen species-induced mutagenesis Tassotto, Mary Lynn Benka 04 September 2002 (has links) Intracellular dNTP pool sizes are highly asymmetric, with dGTP usually comprising 5 to 10% of the sum of the dNTP pools. The work presented in this dissertation addresses the question of whether the underrepresentation of dGTP is related to its potential to be oxidized by reactive oxygen species. 8-oxo-guanine is important in oxidative mutagenesis, and current evidence indicates that this lesion arises in DNA partly through oxidation of dGTP, followed by incorporation of 8-oxo-dGTP into DNA. The bacterial MutT protein and its mammalian homolog catalyze the hydrolysis of 8-oxo-dGTP to 8-oxo-dGMP in vitro. It is a widely accepted premise that the primary function of these enzymes is to remove 8-oxo-dGTP from the nucleotide pool of cells so that it cannot be used as a substrate for DNA synthesis. However, this model has been called into question by observations that some mutT strains of E. coli display a mutator phenotype when grown anaerobically, and by kinetic studies that showed 8-oxo-dGTP to be a poor DNA polymerase substrate. In this study, the dNTP pools of mammalian cells cultured in varying oxygen conditions were measured, with the expectation that the dGTP pool would expand under low oxygen conditions if it were a target for damage by reactive oxygen species. HeLa cells cultured in 2% 0�� showed no change in the dGTP pool when compared to cells cultured in 20% 0��; however, in V79 cells, the dGTP pool did expand in 2% 0��. This result was not specific to the dGTP pool, as pools of dATP and dTTP also increased when V79 cells were cultured at 2% 0��. These results suggest that there may be increased turnover of the dGTP pool when cells are cultured in high oxygen, but these experiments did not address the reason for this oxygen-dependent change. In order to determine whether 8-oxo-dGTP accumulates to levels that are sufficient to cause mutagenesis in cells, an analytical method for the measurement of 8-oxo-dGTP from cell extracts was developed. By use of this method, which involves reversed-phase high performance liquid chromatography coupled with electrochemical detection, no 8-oxo-dGTP was detected in mutT E. coli cells, even when they were cultured in the presence of H��0��. The estimated upper limit of 8-oxo-dGTP in these cells is about 240 molecules per cell, which corresponds to an intracellular concentration of approximately 0.34 ��M. When 8-oxo-dGTP was added at this concentration to an in vitro DNA replication system in which replication errors could be scored as mutations, along with the four normal dNTPs at their estimated intracellular concentrations, there was no detectable effect on the frequency of mutation. Therefore, the presence of 8-oxo-dGTP at physiologically relevant concentrations does not appear to be significantly mutagenic. The results presented in this dissertation suggest that the mechanism by which the MutT enzyme counteracts mutagenesis should be reevaluated. / Graduation date: 2003 Guanosine triphosphate Active oxygen Mutagenesis
3	Oxidative stress and the guanosine nucleotide triphosphate pool implications for a biomarker and mechanism of impaired cell function / Bolin, Celeste Maree. January 2008 (has links) Thesis (Ph. D.)--University of Montana, 2008. / Title from title screen. Description based on contents viewed Aug. 19, 2008. Includes bibliographical references.
4	Effector regulation domains on G[alpha]16 and their role in the activation of phospholipase C[Beta] and other effectors / Yu, Yan Mei. January 2004 (has links) Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2004. / Includes bibliographical references (leaves 94-103). Also available in electronic version. Access restricted to campus users.
5	Ornithine decarboxylase:expression and regulation in rat brain and in transgenic mice Kilpeläinen, P. (Pekka) 25 March 2002 (has links) Abstract Ornithine decarboxylase (EC 4.1.1. 17) is the first and the rate-controlling enzyme in polyamine biosynthesis. It decarboxylates L-ornithine to form diamine putrescine. ODC activity in cells is strictly regulated and one of the central elements of ODC regulation is an inhibitory protein called antizyme. Antizyme binds to ODC, inhibits its activity and targets ODC for the proteasomal degradation. Essentiality of polyamines for the normal cell growth and proliferation is well known. Recently their roles in the regulation of several classes of cation channels have been discovered. Some of these channels are expressed abundantly in the brain, which has increased interest in the polyamine metabolism in the central nervous system. In this study guanosine 5'-triphosphate activatable ODC was detected in the rat brain lysates. This activation was more significant after antizyme was separated from ODC. GTP-activatable ODC was more resistant to heat and displayed higher Vmax than kidney ODC. Previously GTP-activatable ODC had been found in mammalian tissues only in some tumors. ODC and antizyme expression in brain was localized by in situ hybridization and immunocytochemistry. Both proteins displayed wide and largely overlapping expression patterns restricted to neurons. The proteins were localized predominantly to cytoplasm at the most brain regions, but antizyme had a main localization in nuclei in some regions of the brain. In addition, the role of one of the most highly conserved regions in eukaryotic ODCs was studied using site-directed mutagenesis. The aspartate-233 to valine mutation was made and detected to increase Km values for the cofactor PLP and the substrate L-ornithine as well as Ki value for the inhibitor DFMO. In another part of this study a transgenic mouse line expressing ODC under the control of viral promotor was generated. The most significant changes in ODC activity were detected in reproductive organs of male mice. The high number of infertile transgenic males supported earlier reports about the importance of balanced polyamine metabolism for spermatogenesis. Infertility of female mice was increased as well, but the involvement of polyamines remained unproven. Transgenic mice were prone to various pathological conditions such as inflammations and tumour formation, which may be due to deregulated polyamine metabolism. antizyme guanosine triphosphate binding protein polyamines
6	Studies towards a general method for attachment of a nuclear import signal. Stabilization of the m<sub>3</sub>G-Cap. Lindvall, Mattias January 2010 (has links) <p>A synthetic pathway towards the cap-structure of 2,2,7-trimethylguanosine containing a methylene modified triphosphate bridge have been investigated. The modification to the triphosphate bridge is hoped to slow down cap degradation and give the connected oligunucleotide an increased lifetime. This could result in an better understanding of nuclear transport of oligonucleotides and could thereby helping to develop new treatments for different diseases. The synthesis relies on a coupling reaction between the 2,2,7-trimethylguanosine 5’phosphate and 2’-<em>O</em>-methyladenosine with a 5’-pyrophosphate where the central oxygen has been replaced by a methylene group. The reaction pathway consists of 9 steps of which 8 steps have been successfully performed. The last step, which includes a coupling reaction, was attempted but without successful identification and isolation of the cap-structure, and will need further attention. The reaction has been performed in a milligram scale with various yields.</p> / Presentation utförd m3G-cap nuclear transport Duchennes Muscular Dystrophy Guanosine triphosphate analouges Chemistry Kemi
7	Estimating the distribution and production of microplankton in a coastal upwelling front from the cellular content of guanosine-5 triphosphate and adenosine-5 triphosphate Jori, Carol Diane. January 1981 (has links) Thesis (M.S.)--Naval Postgraduate School, 1981. / Cover title. "September 1981." Includes bibliographical references (leaves 108-120).
8	Studies towards a general method for attachment of a nuclear import signal. Stabilization of the m3G-Cap. Lindvall, Mattias January 2010 (has links) A synthetic pathway towards the cap-structure of 2,2,7-trimethylguanosine containing a methylene modified triphosphate bridge have been investigated. The modification to the triphosphate bridge is hoped to slow down cap degradation and give the connected oligunucleotide an increased lifetime. This could result in an better understanding of nuclear transport of oligonucleotides and could thereby helping to develop new treatments for different diseases. The synthesis relies on a coupling reaction between the 2,2,7-trimethylguanosine 5’phosphate and 2’-O-methyladenosine with a 5’-pyrophosphate where the central oxygen has been replaced by a methylene group. The reaction pathway consists of 9 steps of which 8 steps have been successfully performed. The last step, which includes a coupling reaction, was attempted but without successful identification and isolation of the cap-structure, and will need further attention. The reaction has been performed in a milligram scale with various yields. / Presentation utförd m3G-cap nuclear transport Duchennes Muscular Dystrophy Guanosine triphosphate analouges Other Basic Medicine Annan medicinsk grundvetenskap
9	Electrostaticanalisys the Ras active site Khan, Abdul Kareem 05 March 2009 (has links) La preorganització electrostàtica del centre actiu s'ha postulat com el mecanisme genèric de l'acció dels enzims. Així, alguns residus "estratègics" es disposarien per catalitzar reaccions interaccionant en una forma més forta amb l'estat de transició, baixant d'aquesta manera el valor de l'energia dactivació g cat. S'ha proposat que aquesta preorientació electrostática s'hauria de poder mostrar analitzant l'estabilitat electrostàtica de residus individuals en el centre actiu.Ras es una proteïna essencial de senyalització i actúa com un interruptor cel.lular. Les característiques estructurals de Ras en el seu estat actiu (ON) són diferents de les que té a l'estat inactiu (OFF). En aquesta tesi es duu a terme una anàlisi exhaustiva de l'estabilitat dels residus del centre actiu deRas en l'estat actiu i inactiu. / The electrostatic preorganization of the active site has been put forward as the general framework of action of enzymes. Thus, enzymes would position "strategic" residues in such a way to be prepared to catalyze reactions byinteracting in a stronger way with the transition state, in this way decreasing the activation energy g cat for the catalytic process. It has been proposed thatsuch electrostatic preorientation should be shown by analyzing the electrostatic stability of individual residues in the active site.Ras protein is an essential signaling molecule and functions as a switch in thecell. The structural features of the Ras protein in its active state (ON state) are different than those in its inactive state (OFF state). In this thesis, an exhaustive analysis of the stability of residues in the active and inactive Ras active site is performed. dinàmica centre actiu relacions d'estructura activitat preorganització reorganització estat de transició estat actiu estabilitat electrostàtica interacción proteïna-proteïna test de ranks de Wilcoxon P-loop G1 motif HVR metastability RMSD substrate assisted catalysis sequence alignment beta sheet helix Z-test wilcoxon rank test protein-protein interactions electrostatic stability active state dynamics signal transduction electrostatic stabilization ras effectors guanine exchange factor GTPase-activating proteins quantum mechanics/molecular PDLD/S-LRA X-ray crystallography solvation energy free energy perturbation statistical analysis GTP hydrolysis guanosine diphosphate guanosine triphosphate computer simulation thermodynamics protein conformation electrostatics interruptor II interruptor I llaç P motiu G1 HVR (regions altament variables) metaestabilita RMSD catàlisi assistida pel substrat aliniament de seqüència fulla beta hèlix test Z transducció del senyal estabilització electrostàtica efectors de ras factor de bescamvi de guanina proteïnes activadores de l'activitat mecànica quàntica/mecànica PDLD/S-LRA cristalografia de raigs X energia de solvatació perturbació de l'energia lliure anàlisi estadística hidròlisi de GTP difosfat de guanosina trifosfat de guanosina simulació computacional termodinàmica conformació proteïca electrostàtica switch-I switch-II 537 576

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