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101.
The interactions between the protein and the solvent were analyzed, and protein regions with a high density of water molecules, as well as structural water molecules, were determined by using molecular dynamics (MD) simulations. A number of water molecules that were in contact with the protein for the whole trajectory were determined. Their interaction energies and hydrogen bonds with protein residues were analyzed. Altogether, 39, 27, 49, and 32 water molecules bound to the protein were found for trajectories of the free CDK2, CDK2/ATP, CDK2/roscovitine, and CDK2/isopentenyladenine complexes, respectively. Positions of observed water molecules were compared with X-ray crystallography data. Special attention was paid to water molecules in the active site of the enzyme, and especially to the deep pocket, where the N9 roscovitine side-chain is buried. Exchange of active-site water molecules with bulk water through the tunnel from the pocket was observed. In the CDK2/isopentenyladenine complex simulation, two water molecules that arrange interaction between the inhibitor and the enzyme via an H-bond were observed. Two stable water molecules in the trajectory of the free CDK2 were found that occupy the same position as the nitrogens N3 and N9 of the isopentenyladenine or N1 and N6 nitrogens of the adenosine triphosphate (ATP). The positions of structural water molecules were compared with the positions of substrate polar groups and crystallographic water molecules found in the Brookhaven Protein Data Bank for various CDK2 complexes. It was concluded that tracing tightly bound water molecules may substantially help in designing new inhibitors. 相似文献
102.
Knillová J Kolár Z Hlobilková A 《Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia》2003,147(1):11-17
The molecular basis for the transition of carcinoma of the prostate from androgen-dependent to androgen-independent growth is largely unknown. Currently for example, it is not clear whether the androgen-independent phenotype is a result of selection of a subgroup of genetically distinct prostate tumour cells which are already hormone-resistant or a genetic adaptation of prostate tumour cells to the hormone therapy itself. It has also been established that prostate tumour transformation is a result of homeostatic control defects, a line of thinking directed toward elucidating the apoptotic profile of prostate tumour cells that may be important in determining prognosis, response to therapy and illness progression. Main consideration in this part of rewiev is given to the role of tumour suppressor genes pRb and PTEN and also the natural inhibitors of cyclin dependent kinases - proteins p21(Waf1/Cip1) and p27(Kip1). Attention is also given to the role of FAS-mediated pathways in apoptosis induction. 相似文献
103.
The exposure to hypobaric hypoxia increased lipid peroxidation (as indicated by thiobarbituric acid-reactive substances [TBARS] in rat brain. Plasma lactate/pyruvate ratio was used as a marker of hypoxia. We compared the protective effect of -tocopherol with the effect of l-carnitine or phosphocreatine. Rats pretreated with -tocopherol, l-carnitine, or phosphocreatine had lower TBARS levels after the exposure to hypobaric hypoxia. However, lactate/pyruvate ratio was improved only in rats pretreated with l-carnitine or phosphocreatine. We conclude from our data that, contrary to -tocopherol, protective effects of l-carnitine and phosphocreatine administrations are due to their regulation of metabolic reactions during hypobaric hypoxia rather than to their scavenger activity. 相似文献
104.
Allopregnanolone and pregnenolone sulfate, which are neuroactive steroids that differentially modulate the sensitivity of GABA(A) and NMDA receptors, were measured simultaneously in maternal and fetal sera and in amniotic fluid for the first time during the second trimester of gravidity. The study included 33 pregnant women, who underwent cordocentesis due to suspicion of fetal abnormality or alloimmunization. Allopregnanolone concentrations in maternal and fetal sera were similar and close to the previously found levels in healthy controls at 20 weeks of gestation The levels of pregnenolone sulfate in maternal serum were 2-3 times higher and in fetal serum, as much as 10-25 times higher than those found by others in the serum of healthy, non-pregnant women. A positive correlation between maternal and fetal allopregnanolone indicate similar 5alpha-reductase activities or the efficient transport of allopregnanolone between the two subjects. No correlation of pregnenolone sulfate levels between mother and fetus was found. This finding suggests the autonomous production of pregnenolone sulfate in mother and fetus. 相似文献
105.
Charváto J Kasicka V Král V Deyl Z 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2002,770(1-2):165-175
Open-tubular capillary electrochromatography (OT-CEC) was used to study the interactions of synthetic (metallo)porphyrin derivatives (immobilized by physical adsorption to the fused-silica capillary wall) with three aromatic amino acids (phenylalanine, tyrosine, tryptophan), three aliphatic amino acids (beta-alanine, proline, valine) and two oligopeptides (diglycine, triglycine). The effective mobilities of amino acids and peptides measured in OT-CEC mode in the acid and alkaline background electrolytes (BGEs) were compared with those obtained by capillary zone electrophoresis (CZE) in the bare fused-silica capillary in the same BGEs. In this way the influence of the peripheral substituents and the character of the central metal atom in porphyrin derivatives on the interactions with amino acids and peptides in the acid and alkaline media was investigated. Three types of noncovalent interactions, axial ligation to the central metal atom, pi-pi stacking and electrostatic repulsion seem to take part in the interactions of analyzed amino acids and peptides with porphyrin derivatives, resulting in a better separation of these analytes by OT-CEC than by CZE. 相似文献
106.
Capillary electrochromatographic separation of aromatic amino acids possessing peptides using porphyrin derivatives as the inner wall modifiers 总被引:1,自引:0,他引:1
Charvátová J Král V Deyl Z 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2002,770(1-2):155-163
Two different porphyrin derivatives (H2TPP(m-OPh)4 and Rh(III)TPP(m-OPh)4) were investigated with respect to their capability to help resolution of five model aromatic peptides in capillary electrophoresis/open tubular capillary electrochromatography. Though the main separation mechanism was preferentially based on the ionic properties of the separated analytes, involvement of particularly H2TTPP(m-OPh)4-peptide interactions at alkaline pH (8.0) was clearly demonstrated. In combination with Tris-phosphate buffer, a speed up of the separation was observed at pH 2.25 (particularly if Rh(III)TPP(m-OPh)4 was used as capillary coating); in spite of the speed up of the separation the selectivity of the system was sufficient and resulted in a complete separation of the five model peptides. It can be expected that Rh(III)TPP(m-OPh)4 capillary coating in combination with Tris-phosphate buffer can be generally used for a considerable speeding up of lengthy separations of peptides in acidic media with some decrease in the separation power of the system. 相似文献
107.
Ferruccio Guerrieri Martin Kalous Edmondo Adorisio Nicola Turturro Zdenek Drahota Palmiro Cantatore Giuseppe Santoro 《Journal of bioenergetics and biomembranes》1998,30(3):269-276
In liver mitochondria isolated from hypothyroid rats, the rate of ATP synthesis is lower than in mitochondria from normal rats. Oligomycin-sensitive ATP hydrolase activity and passive proton permeability were significantly lower in submitochondrial particles from hypothyroid rats compared to those isolated from normal rats. In mitochondria from hypothyroid rats, the changes in catalytic activities of F0F1-ATP synthase are accompanied by a decrease in the amount of immunodetected -F1, F01-PVP, and OSCP subunits of the complex. Northern blot hybridization shows a decrease in the relative cytosolic content of mRNA for -F1 subunit in liver of hypothyroid rats. Administration of 3,5,3-triodo-L-thyronine to the hypothyroid rats tends to remedy the functional and structural defects of F0F1-ATP synthase observed in the hypothyroid rats. The results obtained indicate that hypothyroidism leads to a decreased expression of F0F1-ATP synthase complex in liver mitochondria and this contributes to the decrease of the efficiency of oxidative phosphorylation. 相似文献
108.
E. Dráberová Zdenek Lukás Dagmar Ivanyi Vladimír Viklický Pavel Dráber 《Histochemistry and cell biology》1998,109(3):231-239
The class III β-tubulin isotype is widely used as a neuronal marker in normal and neoplastic tissues. This isotype was, however,
also immunodetected in certain tumours of non-neuronal origin such as squamous cell carcinoma. Using a newly described monoclonal
antibody we compared the distribution of class III β-tubulin in normal and neoplastic tissues. The TU-20 mouse monoclonal
antibody was prepared against a conserved synthetic peptide from the C-terminus of the human class III β-tubulin isotype,
and its specificity was confirmed by immunoblotting, by competitive enzyme-linked immunosorbent assay and by immunofluorescence
microscopy on cultured cells. In different cell lines of various origins the antibody reacted only with neuroblastoma Neuro-2a
cells and with embryonal carcinoma P19 cells stimulated to neuronal differentiation by retinoic acid. Immunohistochemistry
on formaldehyde-fixed paraffin-embedded normal human tissues revealed the presence of the class III β-tubulin isotype in cell
bodies and processes of neuronal cells in the peripheral and central nervous systems. In other tissues, this β-tubulin isotype
was not immunodetected. Class III β-tubulin was found in all cases of ganglioneuroblastoma, ganglioneuroma, medulloblastoma,
neuroblastoma, sympathoblastoma and in one case of teratoma. In contrast, no reactivity was detected in tumours of non-neuronal
origin, including 32 cases of squamous cell carcinoma. The results indicate a specific TU-20 epitope expression exclusively
in neuronal tissues. The antibody could thus be a useful tool for the probing of class III β-tubulin functions in neurons
as well as for immunohistochemical characterisation of tumours of neuronal origin.
Accepted: 29 July 1997 相似文献
109.