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111.
Optimization of the electrostatic interactions in proteins of different functional and folding type 下载免费PDF全文
Velin Z. Spassov Andrej D. Karshikoff Rudolf Ladenstein 《Protein science : a publication of the Protein Society》1994,3(9):1556-1569
The 3-dimensional optimization of the electrostatic interactions between the charged amino acid residues was studied by Monte Carlo simulations on an extended representative set of 141 protein structures with known atomic coordinates. The proteins were classified by different functional and structural criteria, and the optimization of the electrostatic interactions was analyzed. The optimization parameters were obtained by comparison of the contribution of charge-charge interactions to the free energy of the native protein structures and for a large number of randomly distributed charge constellations obtained by the Monte Carlo technique. On the basis of the results obtained, one can conclude that the charge-charge interactions are better optimized in the enzymes than in the proteins without enzymatic functions. Proteins that belong to the mixed αβ folding type are electrostatically better optimized than pure α-helical or β-strand structures. Proteins that are stabilized by disulfide bonds show a lower degree of electrostatic optimization. The electrostatic interactions in a native protein are effectively optimized by rejection of the conformers that lead to repulsive charge-charge interactions. Particularly, the rejection of the repulsive contacts seems to be a major goal in the protein folding process. The dependence of the optimization parameters on the choice of the potential function was tested. The majority of the potential functions gave practically identical results. 相似文献
112.
P2-fractions were isolated from rat brain, and used to study net taurine transport. The fractions were incubated in increasing concentrations of [3H]taurine and the intraterminal concentration measured by liquid scintillation and amino acid analysis. The membrane potential of the isolated fractions was estimated using86Rb+ as a marker for intracellular K+. Taurine was synthesized in the P2-fraction when incubated in taurine free medium. At external taurine concentrations below 370 M a significant amount of the endogenous taurine was released to the incubation medium. Net taurine uptake into the P2-fraction was achieved at external taurine concentrations exceeding 370 M. The taurine antagonist 6-aminomethyl-3-methyl-4H, 1, 2, 4-benzothiadiazine-1, 1-dioxide (TAG) competitively inhibited taurine and [3H]taurine transport into the P2-fraction. As the external concentration of taurine was increased, the accumulation of86Rb+ into the P2-fraction was facilitated. This indicated an increasing hyperpolarization of the neuronal membrane as taurine transport shifted from release towards uptake. TAG reduced the hyperpolarization that paralleled taurine accumulation, in a dose dependent manner. Our results indicate that relatively low transmembranal gradients of taurine may be maintained by an electrogenic taurine transporter having a large transport capacity. Such a transporter may well serve the needs of osmotic regulation, i.e. to transport large amounts of taurine in any direction across the neuronal membrane. 相似文献
113.
Akemi Tsuda Masatoshi Ito Kazuko Kishi Hideyuki Shiraishi Hideo Tsuda Chuzo Mori 《Neurochemical research》1994,19(1):1-4
To investigate the mechanism of penicillin-induced convulsions, we have studied the effects of penicillin G (PC-G) on GABA-gated chloride ion influx in brain microsac preparations of mice. In the presence of 10–4 M GABA, PC-G inhibited GABA-gated chloride ion influx in a dose-dependent manner. The dose-response curve for GABA in the presence of 10–3 M PC-G was shifted rightward and there was a decrease in maximum response. The inhibitory effects of PC-G were not reversed by RO 15-1788, an antagonist of benzodiazepine (BZ) receptors, but were reversed by washing the microsac membranes. Therefore, PC-G probably exerts its proconvulsant effect by inhibiting GABA-gated chloride ion influx. However, it appears not to act through the BZ receptor of the GABA/BZ receptor complex. 相似文献
114.
Effects of sub-minimal inhibitory concentrations of EDTA on growth of Escherichia coli and the release of lipopolysaccharide 总被引:1,自引:0,他引:1
Christophe Pelletier Pierre Bourlioux Jean van Heijenoort 《FEMS microbiology letters》1994,117(2):203-206
Abstract Release of lipopolysaccharide from E. coli was studied in the presence of sub-minimal inhibitory concentrations of ethylenediaminetetraacetic acid (EDTA). In untreated cells no release was detected with 50 mM Mg2+ in the medium, but a steady release of over 50% of the synthesized lipopolysaccharide was observed with 0.1 mM Mg2+ . EDTA at MIC/8 led to a 2- to 3-fold higher release, presumably by an adjustment of the concentration of unchelated Mg2+ to a value still sustaining normal growth but giving rise to a highly unstable outer membrane. No structural difference was observed between cell-bound and released lipopolysaccharide. 相似文献
115.
The human glucagon receptor encoding gene: structure, cDNA sequence and chromosomal localization 总被引:2,自引:0,他引:2
Si Lok Joseph L. Kuijper Laura J. Jelinek Janet M. Kramer Theodore E. Whitmore Cindy A. Sprecher Shannon Mathewes Francis J. Grant Shaula H. Biggs Gary B. Rosenberg Paul O. Sheppard Patrick J. O''Hara Donald C. Foster Wayne Kindsvogel 《Gene》1994,140(2):203-209
Characterization of the human glucagon-receptor-encoding gene (GGR) should provide a greater understanding of blood glucose regulation and may reveal a genetic basis for the pathogenesis of diabetes. A cDNA encoding a complete functional human glucagon receptor (GGR) was isolated from a liver cDNA library by a combination of polymerase chain reaction and colony hybridization. The cDNA encodes a receptor protein with 80% identity to rat GGR that binds [125I] glucagon and transduces a signal leading to increases in the concentration of intracellular cyclic adenosine 3′,5′-monophosphate. Southern blot analysis of human DNA reveals a hybridization pattern consistent with a single GGR locus. In situ hybridization to metaphase chromosome preparations maps the GGR locus to chromosome 17q25. Analysis of the genomic sequence shows that the coding region spans over 5.5 kb and is interrupted by 12 introns. 相似文献
116.
The spatial distribution and temporal variation of intracellular Ca ion in differentiated Neuroblastoma-Glia Hybridoma 108–15 cells (NG108–15) were investigated using a fluorescence microscope imaging technique. Fura-2 was used as a probe. Electrical current pulses of 10–20 µA were applied to axons connecting to NG cells in order to elicit the influx of Ca ion. The concentration of intracellular Ca is usually 50–80 nM in NG cells in the resting state. Upon stimulation, the Ca level increases by a factor of 2–5. The entry of Ca++ across cell membranes is followed by intracellular diffusion and the propagation of a wave front is clearly seen in digital images. The diffusion constant was calculated to be approximately 1.66×10–6 cm2/sec. This value is about one-fifth of the free diffusion coefficient of Ca ion in aqueous solution (7.82 × 10–6 cm2/sec). Cd ion, at the concentration of 1–2 mM, blocks the influx of Ca as expected whereas the influx is unaffected by TTX at the concentration of 0.1 – 0.2µM. 相似文献
117.
118.
The aim of this study was to characterize the electropharmacological effects of prostacyclin (PGI2) in human atrial fibers and cardiomyocytes. Atrial tissues obtained from the hearts of 28 patients undergoing corrective cardiac surgery were used. Transmembrane action potentials were recorded using a conventional microelectrode technique, and twitch force by a transducer. Effects of PGI2 (1 nM–10 µM) on action potential characteristics and contraction of atrial fibers were evaluated in normal [K]o (4 mM) and high [K]o (27 mM) in the absence and presence of cardiotonic agents. In addition, atrial and ventricular myocytes were isolated enzymatically from atrial tissues and hearts of 4 patients undergoing cardiac transplant. The effects of PGI2 on Na- and Ca-dependent inward currents (INa and ICa) of cardiomyocytes were tested. In 9 human atrial fibers showing fast-response action potentials (mean dV/dtmax = 101 ± 15 Vs–1) in 4 mM [K]o, PGI2 did not influence dV/dtmax of phase 0 depolarization even at 1 µM. However, at a concentration as low as 10 nM, PGI2 depressed spontaneous rhythms or slow-response action potentials in high-K-depolarized fibers. PGI2 also depressed delayed afterdepolarizations and aftercontractions induced by cardiotonic agents. In isolated cardiomyocytes, PGI2 reduced ICa but not INa. The present findings show that, in human atrial fibers and cardiomyocytes, PGI2 induces greater depressant effects on the slow-response action potential, ICa and triggered activity than on the fast-response action potential. It is suggested that PGI2 may act through a selective reduction of transmembrane Ca influx. 相似文献
119.
Giovanna Belmonte Cecilia Pederzolli Peter Maček Gianfranco Menestrina 《The Journal of membrane biology》1993,131(1):11-22
Summary The interaction ofActinia equina equinatoxin II (EqT-II) with human red blood cells (HRBC) and with model lipid membranes was studied. It was found that HRBC hemolysis by EqT-II is the result of a colloid-osmotic shock caused by the opening of toxin-induced ionic pores. In fact, hemolysis can be prevented by osmotic protectants of adequate size. The functional radius of the lesion was estimated to be about 1.1 nm. EqT-II increased also the permeability of calcein-loaded lipid vesicles comprised of different phospholipids. The rate of permeabilization rised when sphingomyelin was introduced into the vesicles, but it was also a function of the pH of the medium, optimum activity being between pH 8 and 9; at pH 10 the toxin became markedly less potent. From the dose-dependence of the permeabilization it was inferred that EqT-II increases membrane permeability by forming oligomeric channels comprising several copies of the cytolysin monomer. The existence of such oligomers was directly demonstrated by chemical cross-linking. Addition of EqT-II to one side of a planar lipid membrane (PLM) increases the conductivity of the film in discrete steps of defined amplitude indicating the formation of cation-selective channels. The conductance of the channel is consistent with the estimated size of the lesion formed in HRBC. High pH and sphingomyelin promoted the interaction even in this system. Chemical modification of lysine residues or carboxyl groups of this protein changed the conductance, the ion selectivity and the current-voltage characteristic of the pore, suggesting that both these groups were present in its lumen. 相似文献
120.
Arthur M. Brown 《The Journal of membrane biology》1993,131(2):93-104
Summary Ion channels are signaling molecules and by them-selves perform no work. In this regard they are un like the usual membrane
enzyme effectors for G proteins. The pathways of G protein receptor, G protein and ion channels are, therefore, purely infor
mational in function. Because a single G protein may have several ion channels as effectors, the effects should be coordinated
and this seems to be the case. Inhibition of Ca2+ current and stimulation of K+ currents would have a greater impact than either alone. Additional flexibility is provided by spontane ous noise in the complexes
of G protein receptor, G protein, and ion channel. By having a non-zero setpoint, the range of control is extended and the
responses become bi-directional. 相似文献