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Mongin Alexander A.; Reddi Jyoti M.; Charniga Carol; Kimelberg Harold K. 《American journal of physiology. Cell physiology》1999,276(5):C1226
Volume-dependent anion channels permeable forCl and amino acids arethought to play an important role in the homeostasis of cell volume.Astrocytes are the main cell type in the mammalian brain showing volumeperturbations under physiological and pathophysiological conditions. Weinvestigated the involvement of tyrosine phosphorylation in hyposmoticmedium-induced[3H]taurine andD-[3H]aspartaterelease from primary astrocyte cultures. The tyrosine kinase inhibitorstyrphostin 23 and tyrphostin A51 partially suppressed thevolume-dependent release of[3H]taurine in adose-dependent manner with half-maximal effects at ~40 and 1 µM,respectively. In contrast, the release ofD-[3H]aspartatewas not significantly affected by these agents in the sameconcentration range. The inactive analog tyrphostin 1 hadno significant effect on the release of both amino acids. The dataobtained suggest the existence of at least two volume-dependent anionchannels permeable to amino acids in astrocyte cultures. One of thesechannels is permeable to taurine and is under the control of tyrosinekinase(s). The other is permeable to both taurine and aspartate, butits volume-dependent regulation does not require tyrosine phosphorylation. 相似文献
44.
Kurukulasuriya R Sorensen BK Link JT Patel JR Jae HS Winn MX Rohde JR Grihalde ND Lin CW Ogiela CA Adler AL Collins CA 《Bioorganic & medicinal chemistry letters》2004,14(9):2047-2050
Biaryl amides derived from a reported series of ureas 1 were evaluated and found to be potent human glucagon receptor antagonists. The benzofuran analogue 6i was administered in Sprague-Dawley rats and blocked the effects of an exogenous glucagon challenge. 相似文献
45.
Synaptotagmin is considered a calcium-dependent trigger for regulated exocytosis. We examined the role of synaptotagmin VII (Syt VII) in the calcium-dependent exocytosis of individual lysosomes in wild-type (WT ) and Syt VII knockout (KO ) mouse embryonic fibroblasts (MEFs) using total internal reflection fluorescence microscopy. In WT MEFs, most lysosomes only partially released their contents, their membrane proteins did not diffuse into the plasma membrane, and inner diameters of their fusion pores were smaller than 30 nm. In Syt VII KO MEFs, not only was lysosomal exocytosis triggered by calcium, but all of these restrictions on fusion were also removed. These observations indicate that Syt VII does not function as the calcium-dependent trigger for lysosomal exocytosis. Instead, it restricts the kinetics and extent of calcium-dependent lysosomal fusion. 相似文献
46.
As part of a project that aims at screening TNA-related oligonucleotide systems in which threose backbone units may have some or all of their oxygen functions replaced by nitrogen, two TNA analogs containing (2'NH)- and (3'NH)-phosphoramidate groups, respectively, in place of phosphodiester groups were synthesized. They show base-pairing properties that are very similar to those of TNA itself. We also synthesized 2',3'-diamino analogs of alpha-L-threofuranosyl mononucleosides, yet attempts to convert them to TNA analogs containing phosphodiamidate linker groups were not successful. Such 2',3'-diamino derivatives of threofuranosyl nucleosides may be of interest, however, as building blocks of TNA analogs that contain non-phosphorous linker groups. 相似文献
47.
Intrinsic contributions of polar amino acid residues toward thermal stability of an ABC-ATPase of mesophilic origin
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Sarin J Raghava GP Chakraborti PK 《Protein science : a publication of the Protein Society》2003,12(9):2118-2120
The nucleotide-binding subunit of phosphate-specific transporter (PstB) from mesophilic bacterium, Mycobacterium tuberculosis, is a unique ATP-binding cassette (ABC) ATPase because of its unusual ability to hydrolyze ATP at high temperature. In an attempt to define the basis of thermostability, we took a theoretical approach and compared amino acid composition of this protein to that of other PstBs from available bacterial genomes. Interestingly, based on the content of polar amino acids, this protein clustered with the thermophiles. 相似文献
48.
Point mutations within the pore region of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel have previously been shown to alter the selectivity of the channel between different anions, suggesting that part of the pore may form an anion 'selectivity filter'. However, the full extent of this selectivity filter region and the location of anion binding sites in the pore are currently unclear. As a result, comparisons between CFTR and other classes of Cl(-) channel of known structure are difficult. We compare here the effects of point mutations at each of eight consecutive amino acid residues (arginine 334-serine 341) in the crucial sixth transmembrane region (TM6) of CFTR. Anion selectivity was determined using patch-clamp recording from inside-out membrane patches excised from transiently transfected mammalian cell lines. The results suggest that selectivity is predominantly controlled by a single site involving adjacent residues phenylalanine 337 and threonine 338, and that the selectivity conferred by this 'filter' region is modified by anion binding to flanking sites involving the more extracellular arginine 334 and the more intracellular serine 341. Other residues within this part of the pore play only minor roles in controlling anion permeability and conductance. Our results support a model in which specific TM6 residues make important contributions to a single, localized anion selectivity filter in the CFTR pore, and also contribute to multiple anion binding sites both within and on either side of the filter region. 相似文献
49.
Denlinger LC Sommer JA Parker K Gudipaty L Fisette PL Watters JW Proctor RA Dubyak GR Bertics PJ 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(3):1304-1311
Activation of the P2X(7) receptor by extracellular nucleotides modulates multiple immune functions, including inflammatory mediator production, membrane fusion events, and apoptosis. Previous studies have revealed that the C terminus of this multimeric cation channel possesses a lipid-interaction motif that has been proposed to regulate receptor function. This domain is homologous to the LPS binding region of the LPS binding protein, and we demonstrated that two basic residues (Arg(578), Lys(579)) within this motif are essential for LPS binding to P2X(7) in vitro. Because P2X(7) can influence LPS action, and because lipid interaction motifs modulate the trafficking of other ion channel-linked receptors, we hypothesized that this motif of P2X(7) is critical for receptor function and trafficking. In these studies we mutated Arg(578) and Lys(579) of P2X(7), and the expression profile, channel activity, and pore formation of the mutant were characterized in transfected human embryonic kidney 293 cells. In contrast with the wild-type receptor, the P2X(7)-R578E/K579E mutant fails to demonstrate surface immunoreactivity despite normal levels of total protein expression. This effect on the mutant receptor is unlikely to result from widespread defects in protein folding, because surface localization, determined using conformation-specific Abs, can be restored by growing the cells at 25 degrees C, conditions that slow receptor recycling. Despite surface expression at reduced temperatures, at 25 degrees C the P2X(7)-R578E/K579E mutant still exhibits greatly reduced sodium, potassium, and calcium channel activity when compared with the wild-type receptor, and cannot induce pore formation. These data suggest that the lipid interaction motif of the P2X(7) C terminus controls receptor trafficking and modulates channel activity. 相似文献
50.
Topological evidences for modelling lipophilicity of a large series of diversed compounds have been provided on the basis of distance-based topological indices. A pool of topological indices along with indicator parameters related to the type of the compounds present in the set of 140 compounds were used for this purpose. The results have shown that topology as well as the type of compounds are the responsible parameters for modelling lipophilicity. 相似文献