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van Kasteren SI Kramer HB Jensen HH Campbell SJ Kirkpatrick J Oldham NJ Anthony DC Davis BG 《Nature》2007,446(7139):1105-1109
One of the most important current scientific paradoxes is the economy with which nature uses genes. In all higher animals studied, we have found many fewer genes than we would have previously expected. The functional outputs of the eventual products of genes seem to be far more complex than the more restricted blueprint. In higher organisms, the functions of many proteins are modulated by post-translational modifications (PTMs). These alterations of amino-acid side chains lead to higher structural and functional protein diversity and are, therefore, a leading contender for an explanation for this seeming incongruity. Natural protein production methods typically produce PTM mixtures within which function is difficult to dissect or control. Until now it has not been possible to access pure mimics of complex PTMs. Here we report a chemical tagging approach that enables the attachment of multiple modifications to bacterially expressed (bare) protein scaffolds: this approach allows reconstitution of functionally effective mimics of higher organism PTMs. By attaching appropriate modifications at suitable distances in the widely-used LacZ reporter enzyme scaffold, we created protein probes that included sensitive systems for detection of mammalian brain inflammation and disease. Through target synthesis of the desired modification, chemistry provides a structural precision and an ability to retool with a chosen PTM in a manner not available to other approaches. In this way, combining chemical control of PTM with readily available protein scaffolds provides a systematic platform for creating probes of protein-PTM interactions. We therefore anticipate that this ability to build model systems will allow some of this gene product complexity to be dissected, with the aim of eventually being able to completely duplicate the patterns of a particular protein's PTMs from an in vivo assay into an in vitro system. 相似文献
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N. J. Oldham E. D. Morgan B. Gobin J. Billen 《Cellular and molecular life sciences : CMLS》1994,50(8):763-765
Totally blind army ants carry out massive and highly organised foraging raids, apparently guided by chemical stimuli. Until now, this phenomenon has not been closely analysed. The existence of a trail pheromone in a postpygidial gland of anAenictus species has been demonstrated and the substances identified as methyl anthranilate and methyl nicotinate The pheromone consists of two parts: a primer effect, caused by methyl nicotinate, which prepares workers to follow trails, but is not itself followed, and a releaser effect, due to methyl anthranilate, which causes trail-following only in conjunction with the primer substance. 相似文献
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This paper presents systematically a method for image compression/decompression viawavelet transform.It consists of filter,quantization and Huffman coding etc..Different methodshave been compared.Finally,some suggestions for further studies are proposed.In fact,the paper isa summary of our recent research. 相似文献
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Superoxide dismutases (SOD) are essential enzymes that eliminate superoxide radical (O2-) and thus protect cells from damage induced by free radicals. The active O2- production and low SOD activity in cancer cells may render the malignant cells highly dependent on SOD for survival and sensitive to inhibition of SOD. Here we report that certain oestrogen derivatives selectively kill human leukaemia cells but not normal lymphocytes. Using complementary DNA microarray and biochemical approaches, we identify SOD as a target of this drug action and show that chemical modifications at the 2-carbon (2-OH, 2-OCH3) of the derivatives are essential for SOD inhibition and for apoptosis induction. Inhibition of SOD causes accumulation of cellular O2- and leads to free-radical-mediated damage to mitochondrial membranes, the release of cytochrome c from mitochondria and apoptosis of the cancer cells. Our results indicate that targeting SOD may be a promising approach to the selective killing of cancer cells, and that mechanism-based combinations of SOD inhibitors with free-radical-producing agents may have clinical applications. 相似文献
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The maltose uptake system of Escherichia coli is a well-characterized member of the ATP-binding cassette transporter superfamily. Here we present the 2.8-A crystal structure of the intact maltose transporter in complex with the maltose-binding protein, maltose and ATP. This structure, stabilized by a mutation that prevents ATP hydrolysis, captures the ATP-binding cassette dimer in a closed, ATP-bound conformation. Maltose is occluded within a solvent-filled cavity at the interface of the two transmembrane subunits, about halfway into the lipid bilayer. The binding protein docks onto the entrance of the cavity in an open conformation and serves as a cap to ensure unidirectional translocation of the sugar molecule. These results provide direct evidence for a concerted mechanism of transport in which solute is transferred from the binding protein to the transmembrane subunits when the cassette dimer closes to hydrolyse ATP. 相似文献
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Iterative methods are popular choices in image reconstruction fields due to their capability of recovering object information from incomplete acquisition data.However,the computation process involves frequent uses of forward and backward projections that are computationally expensive.Past research has proved that a forward projector that can produce high quality images is crucial to achieve a good convergence rate.In this paper a high performance iterative reconstruction framework is introduced,where two mo... 相似文献
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