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71.
72.
ΦX174 lysis protein E-mediated lysis of Escherichia coli is characterized by a protein E-specific fusion of the inner and outer membrane and formation of a transmembrane tunnel structure. In order to understand the fusion process, the topology of protein E within the envelope complex of E. coli was investigated. Proteinase K protection studies showed that, during the time course of protein E-mediated lysis process, more of the fusion protein E-FXa-streptavidin gradually became accessible to the protease at the cell surface. These observations postulate a conformational change in protein E during induction of the lysis process by movement of the C-terminal end of the protein throughout the envelope complex from the inner side to the outer side spanning the entire pore and fusing the inner and outer membranes at distinct areas. The initiation mechanism for such a conformational change could be the cis–trans isomerization of proline residues within α-helical membrane-spanning segments. Conversion of proline 21, presumed to be in the membrane-embedded α-helix of protein E, to alanine, glycine, serine and valine, respectively, resulted in lysis-negative E mutant proteins. Proteinase K accessibility studies using streptavidin as a reporter fused to the P21G mutant protein showed that the C-terminal part of the fusion protein is not translocated to the outer side of the membrane, suggesting that this proline residue is essential for the correct folding of protein E within the cell wall complex of E. coli . Oligomerization of protein P21G-StrpA was not disturbed. 相似文献
73.
Mechanisms of the actions of aromatase inhibitors 4-hydroxyandrostenedione, fadrozole, and aminoglutethimide on aromatase in JEG-3 cell culture 总被引:2,自引:0,他引:2
Wei Yue Angela M. H. Brodie 《The Journal of steroid biochemistry and molecular biology》1997,63(4-6):317-328
Selective inhibition of estrogen production with aromatase inhibitors has been found to be an effective strategy for breast cancer treatment. Most studies have focused on inhibitor screening and in vitro kinetic analysis of aromatase inhibition using placental microsomes. In order to determine the effects of different inhibitors on aromatase in the whole cell, we have utilized the human choriocarcinoma cell line, JEG-3 in culture to compare and study three classes of aromatase inhibitors, 4-hydroxyandrostenedione, fadrozole (CGS 16949A), and aminoglutethimide. Fadrozole is the most potent competitive inhibitor and aminoglutethimide is the least potent among the three. However, stimulation of aromatase activity was found to occur when JEG-3 cells were preincubated with aminoglutethimide. In contrast, 4-OHA and fadrozole caused sustained inhibition of aromatase activity in both JEG-3 cells and placental microsomes, which was not reversed even after the removal of the inhibitors. 4-OHA bound irreversibly to the active site of aromatase and caused inactivation of the enzyme which followed pseudo-first order kinetics. However, 4-OHA appears to be metabolized rapidly in JEG-3 cells. Sustained inhibition of aromatase induced by fadrozole occurs by a different mechanism. Although fadrozole bound tightly to aromatase at a site distinct from the steroid binding site, the inhibition of aromatase activity by fadrozole does not involve a reactive process. None of the inhibitors stimulated aromatase mRNA synthesis in JEG-3 cells during 8 h treatment. The stimulation of aromatase activity by AG appeared to be due to stabilization of aromatase protein. According to these results, 4-OHA and fadrozole would be expected to be more beneficial in the treatment of breast cancer patients than AG. The increase in aromatase activity by AG may counteract its therapeutic effect and might be partially responsible for relapse of breast cancer patients from this treatment. 相似文献
74.
A. Jennifer Rivett Grant G. F. Mason Stuart Thomson Angela M. Pike Peter J. Savory Rachael Z. Murray 《Molecular biology reports》1995,21(1):35-41
The proteasome (multicatalytic proteinase complex) is a large multimeric complex which is found in the nucleus and cytoplasm of eukaryotic cells. It plays a major role in both ubiquitin-dependent and ubiquitin-independent nonlysosomal pathways of protein degradation. Proteasome subunits are encoded by members of the same gene family and can be divided into two groups based on their similarity to the and subunits of the simpler proteasome isolated fromThermoplasma acidophilum. Proteasomes have a cylindrical structure composed of four rings of seven subunits. The 26S form of the proteasome, which is responsible for ubiquitin-dependent proteolysis, contains additional regulatory complexes. Eukaryotic proteasomes have multiple catalytic activities which are catalysed at distinct sites. Since proteasomes are unrelated to other known proteases, there are no clues as to which are the catalytic components from sequence alignments. It has been assumed from studies with yeast mutants that -type subunits play a catalytic role. Using a radiolabelled peptidyl chloromethane inhibitor of rat liver proteasomes we have directly identified RC7 as a catalytic component. Interestingly, mutants in Prel, the yeast homologue of RC7, have already been reported to have defective chymotrypsin-like activity. These results taken together confirm a direct catalytic role for these -type subunits. Proteasome activities are sensitive to conformational changes and there are several ways in which proteasome function may be modulatedin vivo. Our recent studies have shown that in animal cells at least two proteasome subunits can undergo phosphorylation, the level of which is likely to be important for determining proteasome localization, activity or ability to form larger complexes. In addition, we have isolated two isoforms of the 26S proteinase. 相似文献
75.
Angela S. Barbosa Thaís E. Ferraz-Costa Mauro Semer Bernardo Liberman Carlos A. Moreira-Filho 《Human genetics》1995,95(1):63-66
This paper reports a case of XY gonadal dysgenesis in two sisters. Both patients presented an eunochoid female phenotype with normal external genitalia. At laparotomy, the elder sister was found to have bilateral gonadoblastoma. Cytogenetic studies, which included G and C banding and in situ hybridization, showed that the patients had an apparently normal 46, XY karyotype. PCR analyses revealed absence of the conserved portion (HMG box) of the SRY gene and of the Y chromosome pseudoautosomal boundary region sequence in both patients. The presence of the ZFY sequence was detected by Southern hybridization in the two affected sisters. The patients' father (46, XY, no mosaicism detected in peripheral blood lymphocytes) was positive for SRY and ZFY sequences. The occurrence of gonadoblastoma is discussed in terms of the genetic factors that may lead to tumor development. 相似文献
76.
Angela Douglas 《BMJ (Clinical research ed.)》1995,311(7006):672-674
77.
John J. Malinowski Bruce L. Grasberger Gary Trakshel Edward E. Huston Tracey M. Banks Patricia G. Brake Richard B. Ciccarelli Barry N. Jones James A. Koehn Diane Kratz Nicole Lundberg Panayiotis E. Stevis Carla T. Helaszek Mark A. Ator Angela M. Small Wood Travis Stams Byron Rubin Richard S. Alexander 《Protein science : a publication of the Protein Society》1995,4(10):2149-2155
78.
Malcolm N. Jones Philip Manley Angela Holt 《International journal of biological macromolecules》1984,6(2):65-68
The binding of sodium n-dodecyl sulphate to lysozyme has been measured by equilibrium dialysis at 25°C and pH 3.2 over a range of ionic strengts from 0.0119 to 0.2119. Binding isotherms in the region corresponding to ionic binding between the surfactant anions and cationic amino acid residues on the protein have been interpreted in terms of the Hill equation and exhibit positive cooperativity with Hill coefficients in the region of 7–11. The Gibbs energies of binding have been calculated from the Hill binding constants and from the Wyman binding potentials. The stability of the surfactant-protein complexes is discussed in relation to the stability of surfactant micelles. Ionic binding of the surfactant is weakened and hydrophobic binding strengthened by increasing ionic strength. 相似文献
79.
Daniela Cocchi Angela Santagostino Irit Gil-Ad Sergio Ferri Eugenio E. Müller 《Life sciences》1977,20(12):2041-2046
The effect of Leu5-enkephalin on growth hormone (GH) and prolactin (PRL) release was studied in the infant rat and compared to that of morphine. In 10 day-old pups, intracerebroventricular injection of Leu5-enkephalin (50, 75 and 100 μg) resulted in a dose-related increase in plasma GH; morphine was active as GH releaser at the dose of 5 and 10 μg, but not at 2.5 μg. Pretreatment with naloxone (2 mg/kg ip) suppressed the GH-releasing effect of either Leu5-enkephalin (100 μg) or morphine (10 μg). Leu5-enkephalin (75 and 100 μg) induced a rise in plasma PRL which was neither dose-related nor antagonized by naloxone; morphine (5 and 10 μg) was active as PRL releaser and its effect was antagonized by naloxone. These results indicate that: 1) Leu5-enkephalin stimulates both GH and PRL release; 2) the release of GH by Leu5-enkephalin but likely not that of PRL involves specific opiate receptors; 3) morphine releases GH and PRL through specific opiate receptors. 相似文献
80.
The influence of serotonergic and adrenergic antagonists on serum prolactin levels was studied in ketamine anesthetized monkeys. Methysergide, a serotonergic receptor blocker, at 0.035, 0.1 and 1 mg/kg body weight induced a rapid and transient increase in serum prolactin. Cyproheptadine, another serotonergic receptor blocker, at 0.05, 0.5 and 1 mg/kg induced a rapid and sustained increase in serum prolactin. SQ 10631, a third serotonergic receptor blocker, had a minimal effect on increasing basal prolactin levels even at doses as high as 10 mg/kg. Propranolol, a β adrenergic blocker, at a dose of 5 mg/kg induced a small sustained increase in serum prolactin, while a lower dose (1 mg/kg) had a slight but significant effect. Phentolamine, an α adrenergic receptor blocker, at a dose of 5 mg/kg induced a rapid and transient increase in plasma prolactin while a lower dose (1 mg/kg) had no effect. Phenoxybenzamine, a potent α adrenergic receptor blocker, had only a minimal effect on prolactin release even at doses of 3 and 5 mg/kg. It appears that the time course and extent of prolactin release differs among neural antagonists even within the same biogenic amine system. 相似文献