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81.
Free R value: a novel statistical quantity for assessing the accuracy of crystal structures 总被引:32,自引:0,他引:32
Brünger AT 《Nature》1992,355(6359):472-475
The determination of macromolecular structure by crystallography involves fitting atomic models to the observed diffraction data. The traditional measure of the quality of this fit, and presumably the accuracy of the model, is the R value. Despite stereochemical restraints, it is possible to overfit or 'misfit' the diffraction data: an incorrect model can be refined to fairly good R values as several recent examples have shown. Here I propose a reliable and unbiased indicator of the accuracy of such models. By analogy with the cross-validation method of testing statistical models I define a statistical quantity (R(free) (T) that measures the agreement between observed and computed structure factor amplitudes for a 'test' set of reflections that is omitted in the modelling and refinement process. As examples show, there is a high correlation between R(free) (T) and the accuracy of the atomic model phases. This is useful because experimental phase information is usually inaccurate, incomplete or unavailable. I expect that R(free) (T) will provide a measure of the information content of recently proposed models of thermal motion and disorder, time-averaging and bulk solvent. 相似文献
82.
M. T. Santini R. Masella A. Cantafora S. W. Peterson 《Cellular and molecular life sciences : CMLS》1992,48(1):36-39
We have recently demonstrated, using electron paramagnetic resonance (EPR) spectroscopy, that insulin receptor internalization in response to insulin incubation (down-regulation) in human erythrocytes is accompanied by a transient decrease in membrane order, as measured by the 2T order parameter. Since membrane lipids play such an important role in receptor internalization, we investigated the possible effects that an alteration of the normally-occurring lipid profile might have on down-regulation and the concomitant transient decrease in membrane order. Consequently, human erythrocytes enriched with cholesterol and erythrocytes from cirrhotic patients were examined, because both of these groups of cells have a higher cholesterol/phospholipid molar ratio (CH/PL) than controls. The 5-nitroxystearate spin label, which inserts into the lipid bilayer of cell membranes, was used to monitor changes in 2T for a 3-h period at 37°C. We report here that both cholesterol-enriched and cirrhotic erythrocytes do not down-regulate, as demonstrated by binding assays, and that they do not show the typical transient decrease in membrane order observed in controls. The results seem to indicate that a more ordered membrane inhibits internalization of the insulin receptor in erythrocytes, and that an increase in membrane disorder is necessary for insulin receptor down-regulation. 相似文献
83.
The murine Elo (eye lens obsolescence) mutation confers a dominant phenotype characterized by malformation of the eye lens. The mutation maps to chromosome 1, in close proximity to the gamma E-crystallin gene which is the 3'-most member of the gamma-crystallin gene cluster. We have analysed the sequence of this gene from the Elo mouse and identified a single nucleotide deletion which destroys the fourth and last "Greek key" motif of the protein. This mutation is tightly associated with the phenotype, as no recombination was detected in 274 meioses. In addition, the mutant mRNA is present in the affected lens, providing further support for our hypothesis that the deletion is responsible for the dominant Elo phenotype. 相似文献
84.
D. Porquet M. Appel T. Fournier O. Bertaux D. Biou J. Féger 《Cellular and molecular life sciences : CMLS》1992,48(3):257-261
Both in vivo and in vitro models have certain disadvantages for the study of the chronic hepatotoxicity of drugs. The aim of this work was to evaluate a new approach based on an in vivo/in vitro model. After chronic in vivo treatment of rats with Vincamine and Vindeburnol (an eburnamenine derivative which exhibits hepatotoxic properties in man) liver cells were isolated, and functional and metabolic disorders (metabolic utilization of fructose and protein biosynthesis) were studied to determine injury. The results showed no modification of blood parameters, but a direct relationship between the dose of Vindeburnol administered in vivo and the metabolic disorders observed in vitro, evidencing the high sensitivity and reliability of this model. 相似文献
85.
R. Wiesendanger B. Martinoni T. Boller D. Arigoni 《Cellular and molecular life sciences : CMLS》1986,42(2):207-209
Summary Under the action of the appropriate synthase from ripe tomatoes a 11 mixture of (3S, 4R)-[3,4-2H2] and (3R, 4S)-[3,4-2H2]-(2S)-adenosylmethionine is transformed into a 11 mixture of the two meso forms of [2H2]-1-aminocyclopropanecarboxylic acid, a result which proves the operation of an inversion mechanism and which is consistent with direct nucleophilic displacement of the leaving group in the substrate. 相似文献
86.
G. L. Mendz C. R. Middlehurst P. W. Kuchel P. A. Crossie 《Cellular and molecular life sciences : CMLS》1986,42(9):1016-1018
Summary A technique to assay erythrocyte pyrimidine 5-nucleotidase activity in situ using31P nuclear magnetic resonance spectroscopy is presented. The assay is chemically specific, simple and applicable to untreated lysates. A comparison of enzyme levels in normal controls and in multiple sclerosis patients employing the assay yielded no significant differences between both groups. Difficulties encountered in the quantitative analysis of the assay using1H-NMR spectroscopy are briefly discussed. 相似文献
87.
J. -L. Carpentier P. Gorden A. Robert L. Orci 《Cellular and molecular life sciences : CMLS》1986,42(7):734-744
Conclusion The insulin receptor is an integral protein of the plasma membrane of the cell. It is composed of two subunits: an subunit, which binds the hormone, and a subunit which is a tyrosine specific protein kinase capable of undergoing autophosphorylation. These independent subunits are synthesized by way of a higher molecular weight single chain precursor and thus are the product of a single gene29, 49, 85 localized to chromosome 1929, 91. Assuming that the insulin receptor is synthesized in the same fashion as other integral membrane glycoproteins, then the nucleus, the rough endoplasmic reticulum, and the Golgi apparatus are involved in its biosynthesis. Further, there must be some form of transport of the mature receptor subunits to the plasma membrane where they are inserted.By contrast, the endocytotic route involves coated pits, coated vesicles, large clear vesicles or endosomes, multivesicular bodies and other lysosomal forms. In addition, it is possible that some other as yet unidentified organelle is involved in recycling (fig. 8). At the present time, with respect to the insulin receptor, the biosynthetic pathway and the endocytotic pathway appear to be separate. Further, it does not appear that either pathway, i. e. synthesis or endocytosis, exerts a regulatory function over the other. 相似文献
88.
New phytotoxic butenolides produced bySeiridium cardinale,the pathogen of cypress canker disease 总被引:1,自引:0,他引:1
L. Sparapano A. Evidente A. Ballio A. Graniti G. Randazzo 《Cellular and molecular life sciences : CMLS》1986,42(6):627-628
Summary Two new butenolides, seiridin andiso-seiridin, were isolated from culture filtrates ofSeiridium cardinale, the pathogen of cypress canker, a destructive disease ofCupressus and relatedConiferae These metabolites were characterized as 3-methyl-4-(2-hydroxyheptyl)-2(5H)-furanone and its 4-(3-hydroxyheptyl) isomer, respectively. Chlorotic, and necrotic symptoms were produced on leaves of either host or non-host test plants by absorption of 0.3 mg/ml solutions of either compound. These also showed antibacterial activity.This study was supported in part by the National Research Council, Rome (special ad hoc project Chimica fine e secondaria) and in part by the Ministry of Education, Rome. 相似文献
89.
R. S. Verma S. Thomas M. Coleman R. T. Silver H. Dosik 《Cellular and molecular life sciences : CMLS》1986,42(4):440-441
Summary A random distribution of the Y-chromosome at somatic metaphase was found in 50 patients with Ph' positive chronic myelogenous leukemia (CML). Thus, it is concluded that the positive of the Y-chromosome at somatic metaphase does not appear to influence the loss from bone marrow cells. 相似文献
90.
Summary By comparing steroid sulphatase levels per se, and also ratios to -galactosidase, in 6 sets of mice — normal females, entire and castrated males both with and without exogenous testosterone administration — we obtained support for the contention that induction of this enzyme is in part controlled by male hormones. 相似文献