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101.
BACKGROUND: The target of rapamycin (TOR), in complex with the proteins raptor and LST8 (TOR complex 1), phosphorylates the p70S6K and 4E-BP1 to promote mRNA translation. Genetic evidence establishes that TOR complex activity in vivo requires the small GTPase Rheb, and overexpression of Rheb can rescue TOR from inactivation in vivo by amino-acid withdrawal. The Tuberous Sclerosis heterodimer (TSC1/TSC2) functions as a Rheb GTPase activator and inhibits TOR signaling in vivo. RESULTS: Here, we show that Rheb binds to the TOR complex specifically, independently of its ability to bind TSC2, through separate interactions with the mTOR catalytic domain and with LST8. Rheb binding to the TOR complex in vivo and in vitro does not require Rheb guanyl nucleotide charging but is modulated by GTP and impaired by certain mutations (Ile39Lys) in the switch 1 loop. Nucleotide-deficient Rheb mutants, although capable of binding mTOR in vivo and in vitro, are inhibitory in vivo, and the mTOR polypeptides that associate with nucleotide-deficient Rheb in vivo lack kinase activity in vitro. Reciprocally, mTOR polypeptides bound to Rheb(Gln64Leu), a mutant that is nearly 90% GTP charged, exhibit substantially higher protein kinase specific activity than mTOR bound to wild-type Rheb. CONCLUSIONS: The TOR complex 1 is a direct target of Rheb-GTP, whose binding enables activation of the TOR kinase. 相似文献
102.
Ikeda K Tomii K Yokomizo T Mitomo D Maruyama K Suzuki S Higo J 《Protein science : a publication of the Protein Society》2005,14(5):1253-1265
Analysis of the conformational distribution of polypeptide segments in a conformational space is the first step for understanding a principle of structural diversity of proteins. Here, we present a statistical analysis of protein local structures based on interatomic C(alpha) distances. Using principal component analysis (PCA) on the intrasegment C(alpha)-C(alpha) atomic distances, the conformational space of protein segments, which we call the protein segment universe, has been visualized, and three essential coordinate axes, suitable for describing the universe, have been identified. Three essential axes specified radius of gyration, structural symmetry, and separation of hairpin structures from other structures. Among the segments of arbitrary length, 6-22 residues long, the conservation of those axes was uncovered. Further application of PCA to the two largest clusters in the universe revealed local structural motifs. Although some of motifs have already been reported, we identified a possibly novel strand motif. We also showed that a capping box, which is one of the helix capping motifs, was separated into independent subclusters based on the C(alpha) geometry. Implications of the strand motif, which may play a role for protein-protein interaction, are discussed. The currently proposed method is useful for not only mapping the immense universe of protein structures but also identification of structural motifs. 相似文献
103.
OCA4: evidence for a founder effect for the p.D157N mutation of the MATP gene in Japanese and Korean
Inagaki K Suzuki T Ito S Suzuki N Fukai K Horiuchi T Tanaka T Manabe E Tomita Y 《Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society》2005,18(5):385-388
Oculocutaneous albinism type 4 (OCA4) was identified as a rare form of human OCA among a group of autosomal recessive hypopigmentary disorders. Little is known about the prevailing distribution of patients of OCA4 with mutations of the MATP gene, although one Turkish, five German, one Korean, and 18 Japanese patients have been reported so far. The p.D157N mutation was previously reported to be the most frequent (0.389; 14/36) in Japanese patients and was also found in a Korean patient. On the other hand, this mutation has not been found in Turkish and German patients. We therefore investigated haplotypes of the patients who have the p.D157N mutation. The results showed that OCA4 is prevalent in East Asia including Japan and Korea likely as a result of a founder effect for the p.D157N mutation. Furthermore, it is suspected that the p.D157N mutation might have occurred on an ancestral chromosome after the divergence of Orientals and Caucasians. 相似文献
104.
Synthesis and in vivo biodistribution of BPA-Gd-DTPA complex as a potential MRI contrast carrier for neutron capture therapy 总被引:1,自引:0,他引:1
Takahashi K Nakamura H Furumoto S Yamamoto K Fukuda H Matsumura A Yamamoto Y 《Bioorganic & medicinal chemistry》2005,13(3):735-743
p-boronophenylalanine (BPA) conjugated Gd-DTPA complex (3) was synthesized from the active methyne compound 6, the allylic carbonate 7, and BPA by the palladium-catalyzed allylation reaction followed by the DCC coupling reaction. The in vivo biodistribution of complex 3 was evaluated by prompt gamma-ray analysis and alpha-autoradiography using the tumor-bearing rats. High accumulation of gadolinium was observed in the kidney and the %ID values were 0.17 and 0.088 at 20 and 60 min after injection of 3, respectively. The accumulation was also observed in the tumor and the %ID values were 0.010 and 0.0025 at 20 and 60 min after injection, respectively. The visualization experiment of boron distribution in the tumor-bearing rat by alpha-autoradiography indicates that boron was accumulated in the tumor and the intestines at 20 min after injection. 相似文献
105.
Hydroxylation of p-chlorotoluene with heminthiol complexes, Fenton's system and Udenfriend's system was studied and the complexes assessed as models of cytochrome P-450 monooxygenases. Five species of possible hydroxylation products of p-chlorotoluene, namely, p-chlorobenzyl alcohol, 2-chloro-5-methylphenol, p-chlorobenzaldehyde, 4-chloro-2-methylphenol and 5-chloro-2-methylphenol, were studied using high performance liquid chromatography. The oxidation reactions were characterized by the yields of hydroxylation products and the product ratio. The system consisting of hemin and cysteine ethyl ester as well as Udenfriend's system gave relatively high hydroxylation yields and the former only induced a methyl migration during hydroxylation (methyl NIH shift). However, neither Fenton's nor Udenfriend's systems induced a methyl NIH shift. The hemin-thiol complex is thus concluded to be a good chemical model of cytochrome P-450 monooxygenases. 相似文献
106.
Hasegawa T Bando A Tsuchiya K Abe S Okamoto M Kirima K Ueno S Yoshizumi M Houchi H Tamaki T 《Biochimica et biophysica acta》2004,1670(1):19-27
The nonenzymatic and enzymatic formation of reactive oxygen species (ROS) from LY83583 (6-anilino-5,8-quinolinequinone) was investigated by electron paramagnetic resonance (EPR) spectroscopy. In the presence of thiol compounds such as glutathione and L-cysteine, LY83583 underwent a one-electron reduction due to low redox potential (-0.3+/-0.01 V vs. SCE), followed by formation of LY83583 semiquinone anion radical. This species was characterized by EPR spectroscopy under an argon atmosphere at neutral pH. Under an aerobic condition, this species interacts with molecular oxygen to form a superoxide anion radical. GSH-conjugated LY83583 was also identified by NMR and FAB-MS. When LY83583 was applied to PC12 cells, ROS formation was completely inhibited by both the flavoenzyme inhibitor DPI and the DT-diaphorase inhibitor dicumarol. On the other hand, ROS generation occurred independent of intracellular GSH level. These results indicate that LY83583 can generate ROS both enzymatically and nonenzymatically, although the enzymatic formation is dominant over the nonenzymatic system in PC12 cells. 相似文献
107.
108.
Ryo Fujita Takeru Urayama Akimasa Ohmizu Mikihiro Yunoki Shoutaro Tsuji Kazuyoshi Ikuta 《Biologicals》2006,34(3):187-189
The potential contamination of human blood or plasma with prions, such as variant Creuftzfelt-Jacob disease (vCJD), is becoming a serious problem. In this study, we established a Western blot-based detection method for PrP(Sc) (263K) spiked in plasma. Although plasma contains a large amount of protein, specific detection of a small amount of 263K in plasma could be specifically detected only after ultra-centrifugation followed by heat-denaturation of plasma proteins included in the resulting precipitate, before the digestion with proteinase K. 相似文献
109.
The anomeric structure of glycosphingolipids significantly influences their activity to stimulate natural killer T cells. In this study the chemical structure of the galacturonosyl-ceramide in Sphingomonas yanoikuyae, designated GSL-1'sy, was re-examined to prove the anomeric structure of the Dgalacturonic acid (GalA) in the lipid, which was reported as beta-configuration by Naka et al., but was suggested as alpha-configuration in our preliminary study. GSL-1'sy was purified from the bacterial cells with the same procedure as Naka et al. The 1H-NMR analysis of GSL-1'sy revealed that the coupling constant of the anomeric proton of GalA was 3.0 Hz, indicating that GalA in GSL-1'sy is alpha-anomer, the configuration active for the stimulation of natural killer T cells. 相似文献
110.
Yoshimura T Tsuge K Sumi T Yoshiki M Tsuruta Y Abe S Nishino S Sanematsu S Koganemaru K 《Bioscience, biotechnology, and biochemistry》2006,70(4):1026-1028
Marine microorganisms degrading porphyran (POR) were found on the surface of thalli of Porphyra yezoensis. Fifteen crude microorganism groups softened and liquefied the surface of agar-rich plate medium. Among these, 11 microorganism groups degraded porphyran that consisted of sulfated polysaccharide in Porphyra yezoensis. Following isolation, 7 POR-degradable microorganisms were isolated from the 11 POR-degradable microorganism groups. 相似文献