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761.
Thomas Mavromoustakos Efthimia Theodoropoulou Chrysostomos Dimitriou John M. Matsoukas Dimitris Panagiotopoulos Alexandros Makriyannis 《Letters in Peptide Science》1996,3(4):175-180
Summary This study of angiotensin II (ANG II) membrane interactions uses a combination of31P NMR spectroscopy and differential scanning calorimetry (DSC), two valuable and complementary techniques which can provide useful information about the thermotropic and dynamic properties of peptide hormones in membranes. The major conclusion from the calorimetric experiments is that ANG II affects the phase properties of hydrated dipalmitoyl-phosphatidylcholine (DPPC) bilayers by mainly broadening the pretransition area. Preliminary31P NMR data seem to confirm the DSC results by showing that ANG II produces a lowering of the pretransition temperature but affects only minimally the main phase transition. In combination, the results from the two methods may indicate that the hormone produces its effects on the phospholipid head groups while its effects on the bilayer alkyl chains are not significant. Such results can be interpreted to mean that ANG II closely interacts with the phospholipid head groups perhaps up to the level of the interface, but does not enter deeper into the membrane bilayer. 相似文献
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764.
Diomi Mamma Dimitris G. Hatzinikolaou Paul Christakopoulos 《Journal of Molecular Catalysis .B, Enzymatic》2004,27(4-6):183-190
In the presence of rutin as sole carbon source, Penicillium decumbens produces two intracellular β-glucosidases named GI and GII, with molecular masses of 56,000 and 460,000 Da, respectively. The two proteins have been purified to homogeneity. GI and GII composed of two and four equal sub-units, respectively and displayed optimal activity at pH 7.0 and temperature 65–75 °C. Both β-glucosidases were competitively inhibited by glucose and glucono-δ-lactone. GI and GII exhibited broad substrate specificity, since they hydrolyzed a range of (1,3)-, (1,4)- and (1,6)-β-glucosides as well as aryl β-glucosides. Determination of kcat/Km revealed that GII hydrolyzed 3–8 times more efficiently the above-mentioned substrates. The ability of GI and GII to deglycosylate various flavonoid glycosides was also investigated. Both enzymes were active against flavonoids glycosylated at the 7 position but GII hydrolyzed them 5 times more efficiently than GI. Of the flavanols tested, both enzymes were incapable of hydrolyzing quercetrin and kaempferol-3-glucoside. The main difference between GI and GII as far as the hydrolysis of flavanols is concerned, was the ability of GII to hydrolyze the quercetin-3-glucoside. 相似文献
765.
Alba Corman Dimitris C. Kanellis Patrycja Michalska Maria Hggblad Vanesa Lafarga Jiri Bartek Jordi Carreras-Puigvert Oscar Fernandez-Capetillo 《PLoS biology》2021,19(5)
We here conducted an image-based chemical screen to evaluate how medically approved drugs, as well as drugs that are currently under development, influence overall translation levels. None of the compounds up-regulated translation, which could be due to the screen being performed in cancer cells grown in full media where translation is already present at very high levels. Regarding translation down-regulators, and consistent with current knowledge, inhibitors of the mechanistic target of rapamycin (mTOR) signaling pathway were the most represented class. In addition, we identified that inhibitors of sphingosine kinases (SPHKs) also reduce mRNA translation levels independently of mTOR. Mechanistically, this is explained by an effect of the compounds on the membranes of the endoplasmic reticulum (ER), which activates the integrated stress response (ISR) and contributes to the toxicity of SPHK inhibitors. Surprisingly, the toxicity and activation of the ISR triggered by 2 independent SPHK inhibitors, SKI-II and ABC294640, the latter in clinical trials, are also observed in cells lacking SPHK1 and SPHK2. In summary, our study provides a useful resource on the effects of medically used drugs on translation, identified compounds capable of reducing translation independently of mTOR and has revealed that the cytotoxic properties of SPHK inhibitors being developed as anticancer agents are independent of SPHKs.A chemical screen to evaluate how 4100 drugs modulate translation rates confirms mTOR as the main pathway regulating translation and reveals that sphingosine kinase inhibitors downregulate translation via activation of the ER-stress response. Sphingosine kinase inhibitors, including one in clinical trials, activate stress responses and kill cells independently of the cognate target. 相似文献