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101.
Franciskovich JB Masters JJ Tinsley JM Craft TJ Froelich LL Gifford-Moore DS Klimkowski VJ Smallwood JK Smith GF Smith T Towner RR Weir LC Wiley MR 《Bioorganic & medicinal chemistry letters》2005,15(21):4838-4841
Several non-amidino S1 derivatives of the 1,2-diaminobenzene-based scaffold (4) were synthesized and evaluated for their ability to bind to the active site and inhibit the human protease factor Xa. A subset of these compounds were also evaluated for their anticoagulant effects in human plasma as measured by prothrombin time (PT). 相似文献
102.
P pili are protein filaments expressed by uropathogenic Escherichia coli that mediate binding to glycolipids on epithelial cell surfaces, which is a prerequisite for bacterial infection. When a bacterium, attached to a cell surface, is exposed to external forces, the pili, which are composed of approximately 10(3) PapA protein subunits arranged in a helical conformation, can elongate by unfolding to a linear conformation. This property is considered important for the ability of a bacterium to withstand shear forces caused by urine flow. It has hitherto been assumed that this elongation is plastic, thus constituting a permanent conformational deformation. We demonstrate, using optical tweezers, that this is not the case; the unfolding of the helical structure to a linear conformation is fully reversible. It is surmised that this reversibility helps the bacteria regain close contact to the host cells after exposure to significant shear forces, which is believed to facilitate their colonization. 相似文献
103.
The interaction of DNA with amino-functionalized polystyrene particles has been studied by using a dynamic light scattering (DLS) technique. In 10 mM NaBr solution the particles have a hydrodynamic radius of 76 nm and the DNA macromolecule investigated (double stranded) has a hydrodynamic radius of 107 nm. At very low DNA concentrations, DNA adopts a flat conformation on the particle surface. If the DNA concentration is increased above 0.1 microg/mL, the thickness of the DNA layer increases, suggesting the presence of large loops and tails. Although the particles contain primary amino groups, they have a negative net charge under the conditions used in this work. Thus, the driving force for DNA adsorption is not of electrostatic origin but rather due to a hydrophobic effect. Addition of cationic surfactant to the DNA-precoated amino-functionalized particles induces changes in the adsorbed layer conformation, in agreement with the coadsorption of cationic surfactant. 相似文献
104.
105.
Huber PA Birdsey GM Lumb MJ Prowse DT Perkins TJ Knight DR Danpure CJ 《The Journal of biological chemistry》2005,280(29):27111-27120
Although human alanine:glyoxylate aminotransferase (AGT) is imported into peroxisomes by a Pex5p-dependent pathway, the properties of its C-terminal tripeptide (KKL) are unlike those of any other type 1 peroxisomal targeting sequence (PTS1). We have previously suggested that AGT might possess ancillary targeting information that enables its unusual PTS1 to work. In this study, we have attempted to locate this information and to determine whether or not it is a characteristic of all vertebrate AGTs. Using the two-hybrid system, we show that human AGT interacts with human Pex5p in mammalian cells, but not yeast cells. Using (immuno)fluorescence microscopic analysis of the distribution of various constructs expressed in COS cells, we show the following. 1) The putative ancillary peroxisomal targeting information (PTS1A) in human AGT is located entirely within the smaller C-terminal structural domain of 110 amino acids, with the sequence between Val-324 and Ile-345 being the most likely candidate region. 2) The PTS1A is present in all mammalian AGTs studied (human, rat, guinea pig, rabbit, and cat), but not amphibian AGT (Xenopus). 3) The PTS1A is necessary for peroxisomal import of human, rabbit, and cat AGTs, but not rat and guinea pig AGTs. We speculate that the internal PTS1A of human AGT works in concert with the C-terminal PTS1 by interacting with Pex5p indirectly with the aid of a yet-to-be-identified mammal-specific adaptor molecule. This interaction might reshape the tetratricopeptide repeat domain allosterically, enabling it to accept KKL as a functional PTS1. 相似文献
106.
107.
Melander F Andersson T Dib K 《Biochemical and biophysical research communications》2004,317(4):1000-1005
We found that engagement of beta2 integrins on human neutrophils triggered both tyrosine and serine phosphorylation of c-Cbl. Pretreatment of the neutrophils with the broad range protein kinase C (PKC) inhibitor GF-109203X blocked the serine but not the tyrosine phosphorylation of c-Cbl. Moreover, the Src kinase inhibitor PP1 prevented the beta2 integrin-induced tyrosine phosphorylation of c-Cbl but not the simultaneous serine phosphorylation. These results indicate that Src family kinases and PKC can separately modulate the properties of c-Cbl. Indeed, tyrosine kinase-dependent phosphorylation of c-Cbl regulated the ubiquitin ligase activity of that protein, whereas PKC-dependent phosphorylation of c-Cbl had no such effect. Instead, c-Cbl that underwent PKC-induced serine phosphorylation associated with the scaffolding and anti-apoptotic 14-3-3 proteins. Consequently, c-Cbl can independently target proteins for degradation or intracellular localization and may initiate an anti-apoptotic signal in neutrophils. 相似文献
108.
Objective: To identify the determinants of underreporting BMI and to evaluate the possibilities of using self‐reported data for valid obesity prevalence rate estimations. Research Methods and Procedures: A cross‐sectional monitoring health survey was carried out between 1998 and 2002, and a review of published studies was performed. A total of 1809 men and 1882 women ages 20 to 59 years from The Netherlands were included. Body weight and height were reported and measured. Equations were calculated to estimate individuals’ BMI from reported data. These equations and equations from published studies were applied to the present data to evaluate whether using these equations led to valid estimations of the obesity prevalence rate. Also, size of underestimation of obesity prevalence rate was compared between studies. Results: The prevalence of obesity was underestimated by 26.1% and 30.0% among men and women, respectively, when based on reported data. The most important determinant of underreporting BMI was a high BMI. When equations to calculate individuals’ BMI from reported data were used, the obesity prevalence rate was still underestimated by 12.9% and 8.1% of the “true” obesity prevalence rate among men and women, respectively. The degree of underestimating the obesity prevalence was inconsistent across studies. Applying equations from published studies to the present data led to estimations of the obesity prevalence varying from a 7% overestimation to a 74% underestimation. Discussion: Valuable efforts for monitoring and evaluating prevention and treatment studies require direct measurements of body weight and height. 相似文献
109.
110.
CP/MAS 13C NMR spectroscopy was used in combination with spectral fitting to examine the surface structure of hydrated cellulose I fibrils from Halocynthia and Gluconoacetobacter xylinus. To increase the spectral intensities and minimize signal overlap, G. xylinus celluloses site-specifically enriched in 13C either on C4 or on both C1 and C6 were examined. The experimental data showed multiple C4 and C6 signals for the water accessible fibril surfaces in the highly crystalline celluloses. These signal multiplicities were attributed to structural features in the surface layers induced by the fibril interior, and could not be extracted by spectral fitting in celluloses with a lower degree of crystallinity such as cellulose from cotton. 相似文献