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121.
Structure determination of T cell protein-tyrosine phosphatase 总被引:2,自引:0,他引:2
Iversen LF Moller KB Pedersen AK Peters GH Petersen AS Andersen HS Branner S Mortensen SB Moller NP 《The Journal of biological chemistry》2002,277(22):19982-19990
Protein-tyrosine phosphatase 1B (PTP1B) has recently received much attention as a potential drug target in type 2 diabetes. This has in particular been spurred by the finding that PTP1B knockout mice show increased insulin sensitivity and resistance to diet-induced obesity. Surprisingly, the highly homologous T cell protein-tyrosine phosphatase (TC-PTP) has received much less attention, and no x-ray structure has been provided. We have previously co-crystallized PTP1B with a number of low molecular weight inhibitors that inhibit TC-PTP with similar efficiency. Unexpectedly, we were not able to co-crystallize TC-PTP with the same set of inhibitors. This seems to be due to a multimerization process where residues 130-132, the DDQ loop, from one molecule is inserted into the active site of the neighboring molecule, resulting in a continuous string of interacting TC-PTP molecules. Importantly, despite the high degree of functional and structural similarity between TC-PTP and PTP1B, we have been able to identify areas close to the active site that might be addressed to develop selective inhibitors of each enzyme. 相似文献
122.
While the photoreceptor systems of flowering plants have been well studied, the origins of these gene families and their functions are only partially understood. To begin to resolve the evolutionary origins of angiosperm photoreceptor function, we have studied the photomorphogenic responses of the early diverging gymnosperm Ginkgo biloba. Here, we describe the effects of continuous white light, red light, far-red light, and blue light on stem length, chlorophyll accumulation, Lhcb mRNA accumulation, and plastid development. Differences in the efficacy of these light regimes on de-etiolation in Ginkgo suggest separate but complementary roles for red and blue light-sensing systems. Additionally, the unique manner in which developmental regulation occurs in Ginkgo reveals a far-red high irradiance response different from both angiosperm and other gymnosperm species. We conclude from these data that Ginkgo contains a functional complement to both flowering plant type I and type II phytochromes, as well as independent blue light-sensing system(s). The implications of these findings are discussed with respect to the evolution of higher plant photoreceptors. 相似文献
123.
Messenger RNA from young Lotus japonicus roots carrying root nodule primordia appearing after inoculation with Mesorhizobium loti bacteria were used to construct a cDNA expression library. Single-pass sequencing employing colony-polymerase chain reaction (PCR) and analysis of PCR products established a total of 2,397 new expressed sequence tags (ESTs). We have putatively identified 1,236 known and 484 hypothetical proteins coded by the corresponding mRNAs. The remaining cDNAs are unknown (316) or redundant overlapping cDNAs (361). We hope that this batch of ESTs will assist in the recognition of plant genes involved during development of nitrogen-fixing root nodules. 相似文献
124.
A new non-linear normalization method for reducing variability in DNA microarray experiments
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Workman C Jensen LJ Jarmer H Berka R Gautier L Nielser HB Saxild HH Nielsen C Brunak S Knudsen S 《Genome biology》2002,3(9):research0048.1-research004816
Background
Microarray data are subject to multiple sources of variation, of which biological sources are of interest whereas most others are only confounding. Recent work has identified systematic sources of variation that are intensity-dependent and non-linear in nature. Systematic sources of variation are not limited to the differing properties of the cyanine dyes Cy5 and Cy3 as observed in cDNA arrays, but are the general case for both oligonucleotide microarray (Affymetrix GeneChips) and cDNA microarray data. Current normalization techniques are most often linear and therefore not capable of fully correcting for these effects. 相似文献125.
Identification of novel mutations in MLC1 responsible for megalencephalic leukoencephalopathy with subcortical cysts 总被引:3,自引:0,他引:3
Leegwater PA Boor PK Yuan BQ van der Steen J Visser A Könst AA Oudejans CB Schutgens RB Pronk JC van der Knaap MS 《Human genetics》2002,110(3):279-283
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an inherited neurologic disorder with macrocephaly before the age of one and slowly progressive deterioration of motor functions. Magnetic resonance imaging shows diffusely abnormal and swollen white matter of the cerebral hemispheres and the presence of subcortical cysts in the anterior-temporal region and often also in the frontoparietal region. Mutations in the MLC1 gene, encoding a putative membrane protein, have been recently identified as a cause for MLC. Here, we describe 14 new mutations in 18 patients. Two identified polymorphisms lead to alterations of amino acid residues. The role, suggested by others, of a mutation in the MLC1gene in catatonic schizophrenia and the possible function of the MLC1 protein as a cation channel are discussed. 相似文献
126.
127.
Steroid hormones seem to be important for adipose tissue metabolism and accumulation. As progesterone has been suggested to modulate the glucocorticoid effects, the interactions between glucocortioid and progesterone on adipose tissue metabolism were investigated.Forty-eight male Wistar rats were adrenectomized and divided into four groups; controls (treated with vehicle only), dexamethasone treated (10 micro g per rat), progesterone treated (5mg per rat) and the last group received both dexamethasone and progesterone.The dexamethasone-treated group had a significant loss of body weight and smaller intra-abdominal fat depots compared to the control group in addition, dexamethasone increased LPL-activity and increased catecholamine stimulated lipolysis. When progesterone was given concomitantly the dexamethasone effects on adipose tissue mass, LPL-activity and lipolysis were blocked. When given alone progesterone had no influence on body weight, amount of adipose tissue, lipolysis or LPL-activity.These data indicate that progesterone acts as an anti-glucocorticoid in adipose tissue in vivo, thus attenuating the glucocorticoid effect on adipose tissue metabolism. 相似文献
128.
Finding rate constants from experimental data is often difficult because of offset and noise. A computer program was developed to average experimental data points, reducing the effect of noise, and to produce a loge of slope plot – a plot of the natural logarithm of the slope of a curve – eliminating the effect of any offset. If y-values depend exponentially on x-values the loge of slope plot is rectilinear and the slope is equal to the first order rate constant. Therefore the loge of slope plot provides easy identification of exponential sections of any experimental or calculated data, corresponding rate constants, and small changes in the rate constant as exemplified by analysis of titrant added to a batch culture of Aspergillus niger. The loge of slope plot was easily applicable and superior to conventional methods of analysis of exponential decreasing or increasing data. 相似文献
129.
Two folate binding proteins are present in human milk; one of 27 kDa is a cleavage product of the other one (100 kDa) which possesses a hydrophobic membrane anchor. A drastic change of radioligand binding characteristics and appearance of aggregated weak-radioligand affinity forms on gel filtration occurred at low concentrations of both proteins in the absence of Triton X-100 or other amphiphatic substances, e.g. cetyltrimethylammonium and phospholipids. These findings are consistent with a model predicting association between unliganded and liganded monomers resulting in weak-ligand affinity dimers. Amphiphatic substances form micelles and lipid bilayers which could separate hydrophobic unliganded monomers from hydrophilic liganded monomers (monomers become hydrophilic in the liganded state) thereby preventing association between these monomeric forms prevailing at low concentrations of the protein. Bio-Gel P-300 chromatography of the 27 kDa protein revealed a pronounced polymerization tendency, which diminished with decreasing protein concentrations, however, not in the presence of cetyltrimethylammonium. The data could have some bearings on observations indicating that naturally occurring amphiphatic substances, cholesterol and phospholipids, are necessary for the important clustering of membrane folate receptors. 相似文献
130.
Azadeh?BadieeEmail author Hans?Geir?Eiken Vidar?M?Steen Roger?L?vlie 《BMC biotechnology》2003,3(1):23