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11.
Wu CC Li TK Farh L Lin LY Lin TS Yu YJ Yen TJ Chiang CW Chan NL 《Science (New York, N.Y.)》2011,333(6041):459-462
Type II topoisomerases (TOP2s) resolve the topological problems of DNA by transiently cleaving both strands of a DNA duplex to form a cleavage complex through which another DNA segment can be transported. Several widely prescribed anticancer drugs increase the population of TOP2 cleavage complex, which leads to TOP2-mediated chromosome DNA breakage and death of cancer cells. We present the crystal structure of a large fragment of human TOP2β complexed to DNA and to the anticancer drug etoposide to reveal structural details of drug-induced stabilization of a cleavage complex. The interplay between the protein, the DNA, and the drug explains the structure-activity relations of etoposide derivatives and the molecular basis of drug-resistant mutations. The analysis of protein-drug interactions provides information applicable for developing an isoform-specific TOP2-targeting strategy. 相似文献
12.
A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins 总被引:44,自引:0,他引:44
A 73-kilodalton (kD) intracellular protein was found to bind to peptide regions that target intracellular proteins for lysosomal degradation in response to serum withdrawal. This protein cross-reacted with a monoclonal antibody raised to a member of the 70-kD heat shock protein (hsp70) family, and sequences of two internal peptides of the 73-kD protein confirm that it is a member of this family. In response to serum withdrawal, the intracellular concentration of the 73-kD protein increased severalfold. In the presence of adenosine 5'-triphosphate (ATP) and MgCl2, the 73-kD protein enhanced protein degradation in two different cell-free assays for lysosomal proteolysis. 相似文献
13.
Wong J Krisch M Farber DL Occelli F Schwartz AJ Chiang TC Wall M Boro C Xu R 《Science (New York, N.Y.)》2003,301(5636):1078-1080
We report an experimental determination of the phonon dispersion curves in a face-centered cubic (fcc) delta-plutonium-0.6 weight % gallium alloy. Several unusual features, including a large elastic anisotropy, a small-shear elastic modulus C', a Kohn-like anomaly in the T1[011] branch, and a pronounced softening of the [111] transverse modes, are found. These features can be related to the phase transitions of plutonium and to strong coupling between the lattice structure and the 5f valence instabilities. Our results also provide a critical test for theoretical treatments of highly correlated 5f electron systems as exemplified by recent dynamical mean field theory calculations for delta-plutonium. 相似文献
14.
Chiang HC 《Science (New York, N.Y.)》1976,192(4240):675-677
15.
Yao HT Lin JH Chiang MT Chiang W Luo MN Lii CK 《Journal of agricultural and food chemistry》2011,59(8):4306-4314
Adlay ( Coix lachryma-jobi L. var. ma-yuen Stapf) is a grass crop and is reported to protect against various diseases such as cancer. To investigate the effect of the ethanolic extract of adlay bran (ABE) on drug-metabolizing enzymes and glutathione-related antioxidant enzymes in rats, three groups of eight male Sprague-Dawley rats each were fed a control diet or a diet containing 5 or 10% ABE for 4 weeks. Significant decreases in microsomal cytochrome P-450 (CYP) 1A1-catalyzed ethoxyresorufin O-deethylation, CYP2C-catalyzed diclofenac 4-hydroxylation, CYP2D-catalyzed dextromethorphan O-demethylation, and CYP3A-catalyzed testosterone 6β-hydroxylation in the liver and CYP1A1-catalyzed ethoxyresorufin O-deethylation in the lungs of rats fed ABE were observed. Immunoblot analyses also showed decreases of CYP1A1, 1A2, 2C6, 2C11, 2D1, 2E1, 3A1, and 3A2 in the liver and CYP1A1 in the lungs. Furthermore, rats fed the 10% ABE diet had a higher glutathione content and glutathione peroxidase, glutathione reductase, and glutathione S-transferase activities in the lungs, but such an increase was not noted in the liver. Inhibition of various CYP-catalyzed enzyme reactions by ABE in rat and human liver microsomes had also been shown. The results of this study indicate that ABE feeding may suppress CYP enzyme activities and CYP protein expression in the liver and lungs of rats. Moreover, the increase of the antioxidant potential by ABE is tissue-specific. 相似文献
16.
Chung CP Hsu CY Lin JH Kuo YH Chiang W Lin YL 《Journal of agricultural and food chemistry》2011,59(4):1185-1194
Two new lactams, coixspirolactam D (1) and coixspirolactam E (2), and a new spiroenone, coixspiroenone (3), together with seven known compounds, coixspirolactam A (4), coixspirolactam B (5), coixspirolactam C (6), coixlactam (7), coixol (8), ethyl dioxindole-3-acetate (9), and isoindol-1-one (10), and two neolignans, zhepiresionol (11) and ficusal (12), were isolated from the bioactive subfraction of adlay bran ethanolic extract (ABE). Compounds 9 and 10 are the first isolates from natural resources. The structures of new compounds were identified by spectroscopic methods, including infrared (IR) spectrum, 1D and 2D nuclear magnetic resonance (NMR), and mass spectrum (MS). All of the isolated compounds were tested for antiproliferative effects on MCF-7, MDA-MB-231, and T-47D cells. Results showed that compounds 1, 3, 4, 6, and 7 at 50 μM significantly inhibited MCF-7 cell proliferation by 30.2, 19.2, 21.0, 13.5, and 32.4%, respectively; compounds 2, 4, and 7 significantly inhibited T-47D cells at 50 μM by 20.7, 24.8, and 28.9%; and compounds 1, 2, and 12 significantly inhibited MDA-MB-231 cells at 50 μM by 47.4, 25.3, and 69.3%, respectively. In conclusion, ABE has antiproliferative activities, and this effect is partially related to the presence of lactams and spiroenone. 相似文献
17.
Kuo CC Chiang W Liu GP Chien YL Chang JY Lee CK Lo JM Huang SL Shih MC Kuo YH 《Journal of agricultural and food chemistry》2002,50(21):5850-5855
An activity-directed fractionation and purification process was used to identify the antioxidative components of adlay hulls. Hulls of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) were extracted with methanol and then separated into water, 1-butanol, ethyl acetate, and hexane fractions. The 1-butanol-soluble fraction exhibited greater capacity to scavenge 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radicals when compared with fractions soluble in water, ethyl acetate, and hexane phases. The 1-butanol fraction was then subjected to separation and purification using Diaion HP-20 chromatography, silica gel chromatography, and HPLC. Six compounds showing strong antioxidant activity were identified by spectroscopic methods ((1)H NMR, (13)C NMR, IR, and MS) and by comparison with authentic samples to be coniferyl alcohol (1), syringic acid (2), ferulic acid (3), syringaresinol (4), 4-ketopinoresinol (5), and a new lignan, mayuenolide (6). 相似文献
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20.
Atomically uniform silver films grown on highly doped n-type Si(111) substrates show fine-structured electronic fringes near the silicon valence band edge as observed by angle-resolved photoemission. No such fringes are observed for silver films grown on lightly doped n-type substrates or p-type substrates, although all cases exhibited the usual quantum-well states corresponding to electron confinement in the film. The fringes correspond to electronic states extending over the silver film as a quantum well and reaching into the silicon substrate as a quantum slope, with the two parts coherently coupled through an incommensurate interface structure. 相似文献