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排序方式: 共有308条查询结果,搜索用时 31 毫秒
31.
Rife C Schwarzenbacher R McMullan D Abdubek P Ambing E Axelrod H Biorac T Canaves JM Chiu HJ Deacon AM DiDonato M Elsliger MA Godzik A Grittini C Grzechnik SK Hale J Hampton E Han GW Haugen J Hornsby M Jaroszewski L Klock HE Koesema E Kreusch A Kuhn P Lesley SA Miller MD Moy K Nigoghossian E Paulsen J Quijano K Reyes R Sims E Spraggon G Stevens RC van den Bedem H Velasquez J Vincent J White A Wolf G Xu Q Hodgson KO Wooley J Wilson IA 《Proteins》2005,61(2):444-448
32.
33.
Marlene Buchebner Thomas Pfeifer Nora Rathke Prakash G. Chandak Achim Lass Renate Schreiber Adelheid Kratzer Robert Zimmermann Wolfgang Sattler Harald Koefeler Eleonore Fr?hlich Gerhard M. Kostner Ruth Birner-Gruenberger Kyle P. Chiang Guenter Haemmerle Rudolf Zechner Sanja Levak-Frank Benjamin Cravatt Dagmar Kratky 《Journal of lipid research》2010,51(10):2896-2908
Cholesteryl ester (CE) accumulation in macrophages represents a crucial event during foam cell formation, a hallmark of atherogenesis. Here we investigated the role of two previously described CE hydrolases, hormone-sensitive lipase (HSL) and KIAA1363, in macrophage CE hydrolysis. HSL and KIAA1363 exhibited marked differences in their abilities to hydrolyze CE, triacylglycerol (TG), diacylglycerol (DG), and 2-acetyl monoalkylglycerol ether (AcMAGE), a precursor for biosynthesis of platelet-activating factor (PAF). HSL efficiently cleaved all four substrates, whereas KIAA1363 hydrolyzed only AcMAGE. This contradicts previous studies suggesting that KIAA1363 is a neutral CE hydrolase. Macrophages of KIAA1363−/− and wild-type mice exhibited identical neutral CE hydrolase activity, which was almost abolished in tissues and macrophages of HSL−/− mice. Conversely, AcMAGE hydrolase activity was diminished in macrophages and some tissues of KIAA1363−/− but unchanged in HSL−/− mice. CE turnover was unaffected in macrophages lacking KIAA1363 and HSL, whereas cAMP-dependent cholesterol efflux was influenced by HSL but not by KIAA1363. Despite decreased CE hydrolase activities, HSL−/− macrophages exhibited CE accumulation similar to wild-type (WT) macrophages. We conclude that additional enzymes must exist that cooperate with HSL to regulate CE levels in macrophages. KIAA1363 affects AcMAGE hydrolase activity but is of minor importance as a direct CE hydrolase in macrophages. 相似文献
34.
A new approach for freezing of aqueous solutions under active control of the nucleation temperature 总被引:1,自引:0,他引:1
An experimental setup for controlled freezing of aqueous solutions is introduced. The special feature is a mechanism to actively control the nucleation temperature via electrofreezing: an ice nucleus generated at a platinum electrode by the application of an electric high voltage pulse initiates the crystallization of the sample. Using electrofreezing, the nucleation temperature in pure water can be precisely adjusted to a desired value over the whole temperature range between a maximum temperature Tn(max) close to the melting point and the temperature of spontaneous nucleation. However, the presence of additives can inhibit the nucleus formation. The influence of hydroxyethylstarch (HES), glucose, glycerol, additives commonly used in cryobiology, and NaCl on Tn(max) were investigated. While the decrease showed to be moderate for the non-ionic additives, the hindrance of nucleation by ionic NaCl makes the direct application of electrofreezing in solutions with physiological salt concentrations impossible. Therefore, in the multi-sample freezing device presented in this paper, the ice nucleus is produced in a separate volume of pure water inside an electrode cap. This way, the nucleus formation becomes independent of the sample composition. Using electrofreezing rather than conventional seeding methods allows automated freezing of many samples under equal conditions. Experiments performed with model solutions show the reliability and repeatability of this method to start crystallization in the test samples at different specified temperatures. The setup was designed to freeze samples of small volume for basic investigations in the field of cryopreservation and freeze-drying, but the mode of operation might be interesting for many other applications where a controlled nucleation of aqueous solutions is of importance. 相似文献
35.
Lambeck IC Fischer-Schrader K Niks D Roeper J Chi JC Hille R Schwarz G 《The Journal of biological chemistry》2012,287(7):4562-4571
14-3-3 proteins regulate key processes in eukaryotic cells including nitrogen assimilation in plants by tuning the activity of nitrate reductase (NR), the first and rate-limiting enzyme in this pathway. The homodimeric NR harbors three cofactors, each of which is bound to separate domains, thus forming an electron transfer chain. 14-3-3 proteins inhibit NR by binding to a conserved phosphorylation site localized in the linker between the heme and molybdenum cofactor-containing domains. Here, we have investigated the molecular mechanism of 14-3-3-mediated NR inhibition using a fragment of the enzyme lacking the third domain, allowing us to analyze electron transfer from the heme cofactor via the molybdenum center to nitrate. The kinetic behavior of the inhibited Mo-heme fragment indicates that the principal point at which 14-3-3 acts is the electron transfer from the heme to the molybdenum cofactor. We demonstrate that this is not due to a perturbation of the reduction potentials of either the heme or the molybdenum center and conclude that 14-3-3 most likely inhibits nitrate reductase by inducing a conformational change that significantly increases the distance between the two redox-active sites. 相似文献
36.
Albrecht-Buehler G 《Gene》2012,498(1):20-27
The existence of fractal sets of DNA sequences have long been suspected on the basis of statistical analyses of genome data. In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome. Their existence and their fractality may have significant consequences for our understanding of the origin and evolution of genomes. Furthermore, as universal and natural markers they may be used to chart and explore the non-coding regions. 相似文献
37.
Structure and stability of the molybdenum cofactor intermediate cyclic pyranopterin monophosphate 总被引:1,自引:0,他引:1
Jose Angel Santamaria-Araujo Victor Wray Guenter Schwarz 《Journal of biological inorganic chemistry》2012,17(1):113-122
Hydrogenated (reduced) pterins are found in all living organisms, where they are involved in key metabolic processes. Molybdenum
in its biologically active form is bound to a fully reduced tetrahydropyranopterin referred to as a metal-binding pterin (MPT),
forming the so-called molybdenum cofactor (Moco). Cyclic pyranopterin monophosphate (cPMP) is the first isolatable intermediate
in molybdenum cofactor biosynthesis. Here we present for the first time a 13C NMR characterization of an active Moco intermediate. The 13C NMR data for cPMP corroborate previous data showing the tetrahydropyranopterin nature of cPMP and the presence of a gem-diol in the C1′ position of the side chain. The stability of the gem-diol, together with the absence of any observable signal at low field (175–220 ppm), is an indication that the gem-diol is not a chemical artifact, but is chemically stable and not in equilibrium with the keto form. Finally, we have studied
spectrophotometrically the kinetics of cPMP oxidation in the presence of metal centers, chelating agents, and different buffers
and pH values. We found that oxidation is metal-dependent and can be substantially retarded in the presence of EDTA. 相似文献
38.
Zulli AL Aimone LD Mathiasen JR Gruner JA Raddatz R Bacon ER Hudkins RL 《Bioorganic & medicinal chemistry letters》2012,22(8):2807-2810
Optimization of a series of aminomethyl ketone diamine H(3)R antagonists to reduce the brain exposure by lowering the pKa, led to molecules with improved pharmacokinetic properties. Compounds 9, 19, and 25 had high affinity for human H(3)R and demonstrated in vivo H(3)R functional activity in the rat dipsogenia model. Compound 9 displayed modest wake-promoting activity in the rat EEG/EMG model. 相似文献
39.
The balance of hypertrophy and atrophy is critical for the adaptation of cardiac and skeletal muscle mass to the demands of the environment and when deregulated can cause disease. Here we have used a proteomics approach to generate protein reference maps for the mouse heart and skeletal muscle, which provide a molecular basis for future functional and pathophysiological studies. The reference map provides information on molecular mass, pI, and literature data on function and localization, to facilitate the identification of proteins based on their migration in 2-D gels. In total, we have identified 351 cardiac and 284 skeletal muscle protein spots, representing 249 and 214 different proteins, respectively. In addition, we have visualized the protein pattern of mouse heart and skeletal muscle at defined conditions comparing knockout (KO) animals deficient in the sarcomeric protein titin (a genetic atrophy model) and control littermates. We found 20 proteins that were differently expressed linking titin's kinase region to the heat-shock- and proteasomal stress response. Taken together, the established reference maps should provide a suitable tool to relate protein expression and PTM to cardiovascular and skeletal muscle disease using the mouse as an animal model. 相似文献
40.
Bevers LE Hagedoorn PL Santamaria-Araujo JA Magalon A Hagen WR Schwarz G 《Biochemistry》2008,47(3):949-956
Molybdenum (Mo) and tungsten (W) enzymes catalyze important redox reactions in the global carbon, nitrogen, and sulfur cycles. Except in nitrogenases both metals are exclusively associated with a unique metal-binding pterin (MPT) that is synthesized by a conserved multistep biosynthetic pathway, which ends with the insertion and thereby biological activation of the respective element. Although the biosynthesis of Mo cofactors has been intensively studied in various systems, the biogenesis of W-containing enzymes, mostly found in archaea, is poorly understood. Here, we describe the function of the Pyrococcus furiosus MoaB protein that is homologous to bacterial (such as MogA) and eukaryotic proteins (such as Cnx1) involved in the final steps of Mo cofactor synthesis. MoaB reconstituted the function of the homologous Escherichia coli MogA protein and catalyzes the adenylylation of MPT in a Mg2+ and ATP-dependent way. At room temperature reaction velocity was similar to that of the previously described plant Cnx1G domain, but it was increased up to 20-fold at 80 degrees C. Metal and nucleotide specificity for MPT adenylylation is well conserved between W and Mo cofactor synthesis. Thermostability of MoaB is believed to rely on its hexameric structure, whereas homologous mesophilic MogA-related proteins form trimers. Comparison of P. furiosus MoaB to E. coli MoaB and MogA revealed that only MogA is able to catalyze MPT adenylylation, whereas E. coli MoaB is inactive. In summary, MogA, Cnx1G, and MoaB proteins exhibit the same adenylyl transfer activity essential for metal insertion in W or Mo cofactor maturation. 相似文献