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Groll M Schellenberg B Bachmann AS Archer CR Huber R Powell TK Lindow S Kaiser M Dudler R 《Nature》2008,452(7188):755-758
Pathogenic bacteria often use effector molecules to increase virulence. In most cases, the mode of action of effectors remains unknown. Strains of Pseudomonas syringae pv. syringae (Pss) secrete syringolin A (SylA), a product of a mixed non-ribosomal peptide/polyketide synthetase, in planta. Here we identify SylA as a virulence factor because a SylA-negative mutant in Pss strain B728a obtained by gene disruption was markedly less virulent on its host, Phaseolus vulgaris (bean). We show that SylA irreversibly inhibits all three catalytic activities of eukaryotic proteasomes, thus adding proteasome inhibition to the repertoire of modes of action of virulence factors. The crystal structure of the yeast proteasome in complex with SylA revealed a novel mechanism of covalent binding to the catalytic subunits. Thus, SylA defines a new class of proteasome inhibitors that includes glidobactin A (GlbA), a structurally related compound from an unknown species of the order Burkholderiales, for which we demonstrate a similar proteasome inhibition mechanism. As proteasome inhibitors are a promising class of anti-tumour agents, the discovery of a novel family of inhibitory natural products, which we refer to as syrbactins, may also have implications for the development of anti-cancer drugs. Homologues of SylA and GlbA synthetase genes are found in some other pathogenic bacteria, including the human pathogen Burkholderia pseudomallei, the causative agent of melioidosis. It is thus possible that these bacteria are capable of producing proteasome inhibitors of the syrbactin class. 相似文献
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This paper presents an experimental study including visualization on a flat plate closed loop pulsating heat pipes.It consists of a total of 40 channels with square cross section(2 mm×2 mm,165 mm long) machined directly on an aluminum plate(180 mm×120 mm×3 mm) covered by a transparent plate.The working fluid employed is ethanol.As a result,various flow patterns and their transitions are observed and found to be related to the fluid fill ratio,input heat load and the device orientation.Also the operational c... 相似文献
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The degradation of cytosolic proteins is carried out predominantly by the proteasome, which generates peptides of 7-9 amino acids long. These products need further processing. Recently, a proteolytic system was identified in the model organism Thermoplasma acidophilum that performs this processing. The hexameric core protein of this modular system, referred to as tricorn protease, is a 720K protease that is able to assemble further into a giant icosahedral capsid, as determined by electron microscopy. Here, we present the crystal structure of the tricorn protease at 2.0 A resolution. The structure reveals a complex mosaic protein whereby five domains combine to form one of six subunits, which further assemble to form the 3-2-symmetric core protein. The structure shows how the individual domains coordinate the specific steps of substrate processing, including channelling of the substrate to, and the product from, the catalytic site. Moreover, the structure shows how accessory protein components might contribute to an even more complex protein machinery that efficiently collects the tricorn-released products. 相似文献
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Mathematical modeling of pulsating heat pipes through 'first’ principles is a contemporary problem which remains quite elusive. Simplifications and assumptions made in all the modeling approaches developed so far render them unsuitable for engineering design. In this paper, a more realistic modeling scheme is presented which provides considerable try for thought toward the next progressive step. At high enough heat flux level, closed loop pulsating heat pipes experience a bulk internal unidirectional fluid circulation. Under such a condition, conventional two-phaseflow modeling in capillary tubes may be applied. This has been attempted for single-loop PHPs. A homogeneous model and a separated two-fluid flow model based on simultaneous conservation of mass, momentum and energy, have been developed for an equivalent 'open flow' system. The model allows prediction of two-phase flow parameters in each subsection of the device thereby providing important insights into its operation. The concept of 'void fraction constraint'in pulsating heat pipe operation is introduced and its relevance to future modeling attempts is outlined. 相似文献
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不同工质振荡热管的传热性能 总被引:1,自引:1,他引:0
为了解不同工质回路振荡热管运行和传热机理及规律,进行了风冷弯曲封闭循环振荡热管的实验,测定了R123、乙醇和水3种不同工质在振荡热管中不同充注量及不同加热功率下的热阻.结果发现,振荡热管的激励和传热特性与工质的物性包括饱和温度、比热容、汽化潜热及饱和温度下压力随温度的变化率有关,且不同物性在不同工况下作用大小不同,这决定了热管发生振荡的难易和发生振荡后热阻性能的变化. 相似文献
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铜-水振荡热管的传热特性 总被引:5,自引:0,他引:5
测定了风冷垂直放置的蛇形弯曲封闭循环铜一水热管在不同充注率、加热功率下的热阻.根据实验现象及对热阻的比较,分析不同情况下振荡热管的传热特性,并用完全联接的多层前向神经网络和具有动量项的误差反向传递学习算法建立了振荡热管传热性能的人工神经网络理论模型.由于热管在不同充注率时传热机理不同,用统一的神经网络模型难以精确描述,因此建议分段建立理论模型. 相似文献
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Gräwert T Groll M Rohdich F Bacher A Eisenreich W 《Cellular and molecular life sciences : CMLS》2011,68(23):3797-3814
The non-mevalonate pathway of isoprenoid (terpenoid) biosynthesis is essential in many eubacteria including the major human
pathogen, Mycobacterium tuberculosis, in apicomplexan protozoa including the Plasmodium spp. causing malaria, and in the plastids of plants. The metabolic route is absent in humans and is therefore qualified as a promising
target for new anti-infective drugs and herbicides. Biochemical and structural knowledge about all enzymes involved in the
pathway established the basis for discovery and development of inhibitors by high-throughput screening of compound libraries
and/or structure-based rational design. 相似文献
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