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31.
Peteris Prusis Staffan Uhlén Ramona Petrovska Maris Lapinsh Jarl ES Wikberg 《BMC bioinformatics》2006,7(1):167-13
Background
Both direct and indirect interactions determine molecular recognition of ligands by proteins. Indirect interactions can be defined as effects on recognition controlled from distant sites in the proteins, e.g. by changes in protein conformation and mobility, whereas direct interactions occur in close proximity of the protein's amino acids and the ligand. Molecular recognition is traditionally studied using three-dimensional methods, but with such techniques it is difficult to predict the effects caused by mutational changes of amino acids located far away from the ligand-binding site. We recently developed an approach, proteochemometrics, to the study of molecular recognition that models the chemical effects involved in the recognition of ligands by proteins using statistical sampling and mathematical modelling. 相似文献32.
Mihály Purgel Caroline M. Jonsson Ingegärd Andersson Imre Pápai Staffan Sjöberg 《Journal of inorganic biochemistry》2009,103(11):1426-1438
The stoichiometries and stability constants of a series of Al3+-N-phosponomethyl glycine (PMG/H3L) complexes have been determined in acidic aqueous solution using a combination of precise potentiometric titration data, quantitative 27Al and 31P NMR spectra, ATR-FTIR spectrum and ESI-MS measurements (0.6 M NaCl, 25 °C). Besides the mononuclear AlH2L2+, Al(H2L)(HL), and Al(HL)L2−, dimeric Al2(HL)L+ and trinuclear complexes have been postulated.1H and 31P NMR data show that different isomers co-exist in solution and the isomerization reactions are slow on the 31P NMR time scale. The geometries of monomeric and dimeric complexes likely double hydroxo bridged and double phosphonate bridged isomers have been optimized using DFT ab initio calculations starting from rational structural proposals. Energy calculations using the PCM solvation method also support the co-existence of isomers in solutions. 相似文献
33.
Stavermann M Buddrus K St John JA Ekberg JA Nilius B Deitmer JW Lohr C 《Cell calcium》2012,52(2):113-123
Cooling can induce Ca(2+) signaling via activation of temperature-sensitive ion channels such as TRPM8, TRPA1 and ryanodine receptor channels. Here we have studied the mechanism of cooling-evoked Ca(2+) signaling in mouse olfactory ensheathing cells (OECs), a specialized type of glial cells in the olfactory nerve layer of the olfactory bulb. Reducing the temperature from above 30°C to 28°C and below triggered Ca(2+) transients that persisted in the absence of external Ca(2+), but were suppressed after Ca(2+) store depletion by cyclopiazonic acid. Cooling-evoked Ca(2+) transients were present in mice deficient of TRPM8 and TRPA1, and were not inhibited by ryanodine receptor antagonists. Inhibition of InsP(3) receptors with 2-APB and caffeine entirely blocked cooling-evoked Ca(2+) transients. Moderate Ca(2+) increases, as evoked by flash photolysis of NP-EGTA (caged Ca(2+)) and cyclopiazonic acid, triggered InsP(3) receptor-mediated Ca(2+) release at 22°C, but not at 31°C. The results suggest that InsP(3) receptors mediate Ca(2+)-induced Ca(2+) release in OECs, and that this Ca(2+) release is temperature-sensitive and can be suppressed at temperatures above 28°C. 相似文献
34.
Carnrot C Vogel SR Byun Y Wang L Tjarks W Eriksson S Phipps AJ 《Biological chemistry》2006,387(12):1575-1581
Bacillus anthracis, which causes anthrax, has attracted attention because of its potential use as a biological weapon. The risk of multidrug resistance against B. anthracis increases the need for antibiotics with new molecular targets. Nucleoside analogs are well-known antiviral and anticancer prodrugs, and thymidine kinase catalyzes the rate-limiting step in the activation of pyrimidine nucleoside analogs used in chemotherapy. The thymidine kinase gene from B. anthracis Sterne strain (34F2) (Ba-TK) was cloned and expressed in E. coli, and the product was purified and characterized regarding its substrate specificity. Ba-TK phosphorylated pyrimidine nucleosides and all natural nucleoside triphosphates served as phosphate donors. Size exclusion chromatography indicated a dimeric form of Ba-TK, regardless of the presence of ATP. Thymidine was the most efficient substrate with a low K(m) value (0.6 microM) and a V(max) of 3.3 micromol dTMP mg(-1) min(-1), but deoxyuridine (K(m)=4.2 microM, V(max)=4.1 micromol dUMP mg(-1) min(-1)) was also a good substrate. Several pyrimidine analogs were also tested and analogs with 5-position modifications showed higher activities compared to analogs with 3'- and N3-position modifications. Deoxyuridine analogs were the most potent inhibitors of B. anthracis growth in vitro. These results may be used to guide future development of nucleoside analogs against B. anthracis. 相似文献
35.
Progenitor cells in the mouse olfactory epithelium generate over a thousand subpopulations of neurons, each expressing a unique odorant receptor (OR) gene. This event is under the control of spatial cues, since neurons in different epithelial regions are restricted to express region-specific subsets of OR genes. We show that progenitors and neurons express the LIM-homeobox gene Lhx2 and that neurons in Lhx2-null mutant embryos do not diversify into subpopulations expressing different OR genes and other region-restricted genes such as Nqo1 and Ncam2. Lhx2-/- embryos have, however, a normal distribution of Mash1-positive and neurogenin 1-positive neuronal progenitors that leave the cell cycle, acquire pan-neuronal traits and form axon bundles. Increased cell death in combination with increased expression of the early differentiation marker Neurod1, as well as reduced expression of late differentiation markers (Galphaolf and Omp), suggests that neuronal differentiation in the absence of Lhx2 is primarily inhibited at, or immediate prior to, onset of OR expression. Aberrant regional expression of early and late differentiation markers, taken together with unaltered region-restricted expression of the Msx1 homeobox gene in the progenitor cell layer of Lhx2-/- embryos, shows that Lhx2 function is not required for all aspects of regional specification of progenitors and neurons. Thus, these results indicate that a cell-autonomous function of Lhx2 is required for differentiation of progenitors into a heterogeneous population of individually and regionally specified mature olfactory sensory neurons. 相似文献
36.
Tandem duplication induced by an unusual ampA1-, ampC-transducing lambda phage: A probe to initiate gene amplification 总被引:3,自引:0,他引:3
Thomas Edlund Thomas Grundström Glenn R. Björk Staffan Normark 《Molecular & general genetics : MGG》1980,180(2):249-257
Summary Secondary attachment site -lysogens were isolated in an Escherichia coli strain carrying multiple tandem 9.8 kb repeats. The repeat carried the structural gene for chromosomal -lactamase, ampC. One lysogen produced lysates with amp-transducing activity. Three types of phages with different densities were obtained from this lysogen. The one with the lowest density was found to be a helper cI857S7 phage. The other two phages showed identical restriction endonuclease fragmentation patterns. The difference in density was due to the presence or absence of phage tail. In damp the right cohesive end segment was deleted in a random fashion with the majority ending between 81.0% and 82.4% of . The chromosomal segment of damp was most likely located at the attachment site. The damp DNA was compared to that of a ColE1 hybrid carrying the chromosomal amp segment and a ColE1 hybrid carrying the same 9.8 kb amp repeat as the lysogen from which damp was isolated. It was found that the chromosomal part of damp constituted 9.8 kb, i.e. the size of one repeat. Moreover, the novel joint between adjacent repeats was present. In a attB-deleted E. coli K-12 strain, lysogenic for damp, highly ampicillin-resistant mutants occurred at an exceedingly high frequency. They were found to contain in the chromosome an amplified 9.8 kb repeat. This suggested that integration of the novel joint from damp into the amp region gives rise to an amplifiable duplication. In E. coli lysogenized for damp at attB highly ampicillin-resistant clones were also found at a high frequency. These clones carried multiple tandem repeats of damp DNA, each with an intact right end segment. 相似文献
37.
38.
The elaborate male displays and plumage ornaments in the African widowbirds and bishops (Euplectes spp.) have inspired classic studies on mating systems and sexual selection. In order to study the extreme divergence in ornament design and expression in this group, we present and discuss a well-supported molecular phylogeny of the genus and its placement within the Ploceinae subfamily. Parsimony and Bayesian analyses were performed on 2557bp of mitochondrial DNA (ATP6, Cyt b, ND2 and ND3) and a nuclear intron (G3PDH). All 17 Euplectes species, and 31 of 51 suggested subspecies, were included, as well as eight Ploceinae outgroups from four genera (Amblyospiza, Ploceus, Quelea and Foudia). Our results show monophyly of Euplectes, but not of the intrageneric groupings of bishops and widowbirds. Most notably, the Red-collared Widowbird E. ardens belongs to a subclade of bishops, and not to the sister subclade of 'true' widowbirds. Furthermore, the two bishops E. afer and E. aureus represent lineages that branched off before this basal split, which also refutes the proposed superspecies of E. afer and E. diadematus. Also somewhat surprisingly, and despite the striking plumage similarities among the red bishops, E. franciscanus is not closely related to either E. nigroventris or E. orix (of which it until recently was considered a subspecies). Finally, the Mountain Marsh Widowbird E. psammocromius is likely closest to the Long-tailed Widowbird E. progne, and not, as previously thought, to the Marsh Widowbird E. hartlaubi. 相似文献
39.
We use the assignment technique and a new approach, the 'novel allele technique', to detect sex-biased dispersal in great reed warblers Acrocephalus arundinaceus. The data set consisted of immigrants and philopatric birds in a semi-isolated population in Sweden scored at 21 microsatellite loci. Fourteen cohorts were represented of which the four earliest were used to define a reference population. Female immigrants had lower assignment probability than males (i.e. were less likely to have been sampled in the reference population), and carried the majority of 'novel alleles' (i.e. alleles observed in the population for the first time). The difference in number of novel alleles between sexes was caused by a strong over-representation of females among the few individuals that carried several novel alleles, and there was a tendency for a corresponding female bias among individuals with low assignment probabilities. Immigrant males had similar or lower reproductive success than females. These results lead us to conclude that important interregional gene flow in great reed warblers depends on relatively few dispersing females, and that the novel allele technique may be a useful complement to the assignment technique when evaluating dispersal patterns from temporally structured data. 相似文献
40.
Isolation and characterization of DNA repetitions carrying the chromosomal beta-lactamase gene of Escherichia coli K-12. 总被引:32,自引:0,他引:32
Thomas Edlund Thomas Grundström Staffan Normark 《Molecular & general genetics : MGG》1979,173(2):115-125
Summary A ColE1 hybrid plasmid, pNU1, carrying the amp operon coding for chromsomal -lactamase was isolated from the Clarke and Carbon collection and physically mapped. The physical location of ampC within this plasmid was further deduced by in vitro cloning.By reciprocal recombination between pNU1 and chromosome of two unstable -lactamase hyperproducing E. coli K-12 mutants a large plasmid from each mutant was obtained. The respective plasmid was physically mapped and found to contain five and two repeated DNA segments. The repetitions within each plasmid were equal in size, 9,800 bp and 11,900 bp respectively and were organized in tandem. The end points of the repeats were different in the two plasmids but shared a DNA segment carrying the ampC gene. The chromosomal DNA of the -lactamase hyperproducing E. coli mutants were found to contain an amplified DNA segment equal in size to the repeated unit found in the respective plasmid. The data shows that up to 10 identical repeats organized in tandem can be generated by a normal mutation frequency in E. coli. 相似文献