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91.
The progress achieved by several groups in the field of computational protein design shows that successful design methods include two major features: efficient algorithms to deal with the combinatorial exploration of sequence space and optimal energy functions to rank sequences according to their fitness for the given fold. 相似文献
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González Díaz H Olazabal E Castañedo N Sánchez IH Morales A Serrano HS González J de Armas RR 《Journal of molecular modeling》2002,8(8):237-245
A novel method for in silico selection of fluckicidal drugs is introduced. Two QSARs that permit us to discriminate between fasciolicide and non-fasciolicide drugs (the first) and to outline some conclusions about the possible mechanism of action of a chemical (the second) are performed. The first model correctly classified 93.85% of compounds in the training series and 89.5% of the compounds in the predicting one. This model correctly classified 87.7, 93.8, 92.2 and 93.9% of compounds in leave- n-out cross validation procedures when n takes values from 2 to until 6. The model seems to be stable in around 92% of good classification in leave- n-out cross validation analysis when n>6. The second model correctly classified 70% of non-fasciolicide compounds, 85.71% of beta-tubulin inhibitors and 100% of proton ionophores in the training set. This model recognizes as proton ionophores 100% of any nitrosalicylanilides in the predicting series. Both models have a low p-level <0.05. Finally, the experimental assay of six organic chemicals by an in vivo test permit us to carry out an assessment of the model with a fairly good 100% agreement between experiment and theoretical prediction. 相似文献
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Protein kinases dedicated to the phosphorylation of SR proteins have been implicated in the processing and nuclear export of mRNAs. Here we demonstrate in Saccharomyces cerevisiae their participation in cation homeostasis. A null mutant of the single yeast SR protein kinase Sky1p is viable but exhibits increased tolerance to diverse toxic cations such as Na(+), Li(+), spermine, tetramethylammonium, hygromycin B and Mn(2+). This pleiotropic phenotype correlates with reduced accumulation of cations, suggesting a decrease in membrane electrical potential. Genetic analysis and Rb(+) uptake measurements indicate that Sky1p modulates Trk1,2, the high-affinity K(+) uptake system of yeast and a major determinant of membrane potential. 相似文献
97.
Pérez-Castiñeira JR Alvar J Ruiz-Pérez LM Serrano A 《Biochemical and biophysical research communications》2002,291(3):567-573
The BAZF gene has recently been identified as a novel homologue of the BCL6 oncogene. Here we cloned the human BAZF gene using murine BAZF as a probe. The predicted amino acid sequence was 91% identical to that of murine BAZF. The BTB/POZ and zinc finger domains were almost completely conserved between human and murine BAZF. Fluorescence in situ hybridization analysis revealed that the human BAZF gene is located on chromosome 17p13.1. Although expression of human BAZF mRNA was ubiquitously detected in human tissues, abundant expression was detected in heart and placenta. BAZF mRNA was expressed in some immature B cell lines and erythroleukemia cell lines. The expression in a human erythroleukemia cell line, HEL cells, was upregulated during megakaryocytic differentiation induced by 12-O-tetradecanoyl-phorbol-13-acetate. These expression patterns of BAZF mRNA suggest that BAZF may regulate differentiation in stages or lineages that are different from those regulated by BCL6. 相似文献
98.
Vera-Gil A Pérez-Castejón MC Lahoz M Aisa J Recreo MP Serrano P Pes N 《Histology and histopathology》2003,18(2):467-473
We have studied the autoradiographic uptake of 65Zn in the cerebellum and brainstem of the rat, contrasting these results with Timm's positivity in these structures. Both, autoradiographic uptake and histochemical positivity, have demonstrated Zinc in a location that could be accepted as in climbing fibres and glomeruli of the cerebellum cortex, and also in brainstem neurons that project their axons to the cerebellum cortex, suggesting a circuit where zinc may act as a neuromodulator. 相似文献
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Cruz A Worthman LA Serrano AG Casals C Keough KM Pérez-Gil J 《European biophysics journal : EBJ》2000,29(3):204-213
Suspensions of dipalmitoylphosphatidylcholine (DPPC) bilayers containing 5, 10 or 20% (w/w) surfactant protein SP-B have
been reconstituted and spread at air-liquid interfaces. Compression isotherms of DPPC/SP-B monolayers spread from these preparations
were qualitatively comparable to the isotherms of the corresponding DPPC/SP-B monolayers spread from solvents. SP-B was squeezed-out
at higher pressures from vesicle-spread films than from solvent-spread monolayers. SP-B caused a marked decrease on the rate
of relaxation of DPPC collapse phases to equilibrium pressures in all the lipid/protein films assayed. This stabilizing effect
was higher in vesicle-spread than in solvent-spread monolayers. Inclusion in the films of traces of the fluorescent probe
NBD-PC (1 mol%) and use of a fluorescent derivative of SP-B labeled with a rhodamine derivative, Texas Red, allowed for direct
observation of protein and lipid domains at the interface by epifluorescence microscopy. Upon compression, SP-B altered the
packing of phospholipids in the bilayer-spread films, observed as a SP-B-induced reduction of the area of liquid-condensed
domains, in a way similar to its effect in solvent-spread monolayers. SP-B was not associated with condensed regions of the
films. Fluorescence images from vesicle-spread films showed discrete fluorescent aggregates that could be consistent with
the existence of lipid-protein vesicles in close association with the monolayer. Both the retention of SP-B at higher surface
pressures and the greater stability of collapse phases of DPPC/SP-B films prepared by spreading from liposomes in comparison
to those spread from solvents can be interpreted as a consequence of formation of complex bilayer-monolayer interacting systems.
Received: 1 December 1999 / Revised version: 2 March 2000 / Accepted: 2 March 2000 相似文献