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排序方式: 共有2035条查询结果,搜索用时 281 毫秒
1.
Dr. Adarshi P. Welegedara Dr. Ansis Maleckis Ruchira Bandara Dr. Mithun C. Mahawaththa Iresha Dilhani Herath Yi Jiun Tan Dr. Angeliki Giannoulis Prof. Daniella Goldfarb Prof. Gottfried Otting Prof. Thomas Huber 《Chembiochem : a European journal of chemical biology》2021,22(8):1480-1486
The selenol group of selenocysteine is much more nucleophilic than the thiol group of cysteine. Selenocysteine residues in proteins thus offer reactive points for rapid post-translational modification. Herein, we show that selenoproteins can be expressed in high yield and purity by cell-free protein synthesis by global substitution of cysteine by selenocysteine. Complete alkylation of solvent-exposed selenocysteine residues was achieved in 10 minutes with 4-chloromethylene dipicolinic acid (4Cl-MDPA) under conditions that left cysteine residues unchanged even after overnight incubation. GdIII−GdIII distances measured by double electron–electron resonance (DEER) experiments of maltose binding protein (MBP) containing two selenocysteine residues tagged with 4Cl-MDPA-GdIII were indistinguishable from GdIII−GdIII distances measured of MBP containing cysteine reacted with 4Br-MDPA tags. 相似文献
2.
Dr. Raysa Khan Tareque Dr. Storm Hassell-Hart Dr. Tobias Krojer Dr. Anthony Bradley Dr. Srikannathasan Velupillai Dr. Romain Talon Dr. Michael Fairhead Dr. Iain J. Day Kamlesh Bala Dr. Robert Felix Dr. Paul D. Kemmitt Prof. Paul Brennan Prof. Frank von Delft Dr. Laura Díaz Sáez Prof. Kilian Huber Prof. John Spencer 《ChemMedChem》2020,15(24):2513-2520
Combined photochemical arylation, “nuisance effect” (SNAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with SNAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified. 相似文献
3.
Alfonso Martín-Bernab Josep Tarrag-Celada Valrie Cunin Sylvie Michelland Roldn Corts Johann Poignant Cyril Boyault Walid Rachidi Sandrine Bourgoin-Voillard Marta Cascante Michel Seve 《International journal of molecular sciences》2021,22(7)
Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies. 相似文献
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Continuous simulation is performed using the US Environmental Protection Agency (USEPA) Storm Water Management Model (SWMM) to evaluate regional differences around the United States in hydrologic and water quality performance of wet-weather controls. Controls are characterised as being limited by peak inflow rate (i.e. any device with little or no storage, such as screens, filters and some proprietary devices) or by storage capacity (e.g., ponds, tanks). For flow-limited devices, results are presented in the form of percentage of annual runoff volume captured (passing through the device) for a given inflow capacity. For storage-limited devices, results are presented in two forms: percentage of annual runoff volume captured as a function of unit basin size and drawdown (drain) time, and as a percentage of total suspended solids captured, for the same two variables. Regional differences are apparent, driven mainly by variations in rainfall patterns around the country. 相似文献
7.
Magnus Rnning Florian Huber Hilde Meland Hilde Venvik De Chen Anders Holmen 《Catalysis Today》2005,100(3-4):249-254
In order to investigate the effect of cerium oxide on Cu–Zn-based mixed-oxide catalysts four catalyst samples were characterized by means of XRD, in situ XANES and thermogravimetric analysis. The activity of the catalyst samples was tested for the forward water–gas shift reaction. Cerium oxide was found to increase the crystallinity of the ZnO phase indicating a segregation of the Cu and ZnO phases. The TOF of the water–gas shift reaction based on chemisorption data was found to be independent of composition and preparation conditions of the four catalyst samples. In contrast, the catalyst stability depends on composition and preparation conditions. Cerium oxide impregnated before calcination of the hydrotalcite-based Cu–Zn precursors leads to a more stable water–gas shift catalyst. 相似文献
8.
Multiobjective evaluation of advanced manufacturing system technology investments with risk 总被引:2,自引:0,他引:2
Advanced manufacturing system technologies are difficult to evaluate using ordinary financial measures owing to the presence of risk and significant intangible factors. In this paper a methodology is proposed that quantifies financial, strategic, and tactical attributes of each alternative. Attribute values are denned for each period of project life. Both project life and attributes are treated as random variables. Attributes are discounted to the current time and the multiple objectives are combined by composite programming. The distribution of the combined objective is estimated. The procedure is demonstrated on an actual case study. 相似文献
9.
J Lorenz K Wilhelm M Kessler C Peschel U Schwulera R Lissner WG Struff E Huland C Huber WE Aulitzky 《Canadian Metallurgical Quarterly》1996,2(7):1115-1122
Safety, local and systemic immunomodulation, and tumor response to treatment with aerosolized natural interleukin 2 (nIL-2) applied five times a day were studied in a Phase I trial in 16 patients with pulmonary malignancies refractory to conventional therapy. The toxicity of inhaled nIL-2 was different from that observed after systemic administration. Reversible airway irritation causing a nonproductive cough represented the dose-limiting toxicity. Mild to moderate reduction of the vital capacity and forced expiratory volume (FEV1) with minor effects on relative FEV1, peak expiratory flow, airway resistance, and PaO2 was experienced by individual patients. In 14 patients suffering from pulmonary metastases due to renal cell cancer, one durable complete response, one partial response, and one mixed response were observed. Inhalation of nIL-2 aerosol resulted in a dose-dependent expansion of pulmonary immunocompetent cells in bronchoalveolar lavage fluid. Posttreatment bronchoalveolar lavage showed an activated lymphocyte phenotype with increased HLA-DR expression. The only systemic biological effect detectable in peripheral blood was a marked increase of soluble interleukin 2 receptor serum levels. We conclude that treatment with aerosolized nIL-2 is an effective means for site-specific immunomodulation and deserves further investigation for the treatment of malignant and inflammatory lung disease. 相似文献
10.
A Burger D Voges P Demange CR Perez R Huber R Berendes 《Canadian Metallurgical Quarterly》1994,237(4):479-499
Annexin V binds to phospholipids in a calcium-dependent manner and exhibits calcium channel activity in vitro. We prepared a variety of mutants yielding information about the structure-function relationship of the ion channel activity. All mutants were characterized by X-ray crystallography, electron microscopy and electrophysiological measurements. Their structures are insignificantly changed whereas their electrophysiological properties are drastically different. Glu95, located in the central hydrophilic pore of the molecule, is crucial for the ion selectivity filter as its exchange leads to reduced calcium and increased sodium conductance. The removal of Glu17, located on the protein surface and far from the ion conduction pathway, leads to the appearance of a second conductance level of 9 pS in addition to the conductance level of about 30 pS in the wild-type molecule. This was also the case for Glu78, which is part of a weak calcium binding site. The exchange of Glu17 and Glu78 produced a mutant retaining only the smaller conductance level. We conclude that these two residues influence the angle between the two halves of the molecule, which determines the diameter of the ion conduction pathway, thereby leading to the occurrence of a second conductance level. 相似文献