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21.
Solution structure of the potassium channel inhibitor agitoxin 2: caliper for probing channel geometry. 总被引:5,自引:1,他引:4 下载免费PDF全文
A. M. Krezel C. Kasibhatla P. Hidalgo R. MacKinnon G. Wagner 《Protein science : a publication of the Protein Society》1995,4(8):1478-1489
The structure of the potassium channel blocker agitoxin 2 was solved by solution NMR methods. The structure consists of a triple-stranded antiparallel beta-sheet and a single helix covering one face of the beta-sheet. The cysteine side chains connecting the beta-sheet and the helix form the core of the molecule. One edge of the beta-sheet and the adjacent face of the helix form the interface with the Shaker K+ channel. The fold of agitoxin is homologous to the previously determined folds of scorpion venom toxins. However, agitoxin 2 differs significantly from the other channel blockers in the specificity of its interactions. This study was thus focused on a precise characterization of the surface residues at the face of the protein interacting with the Shaker K+ channel. The rigid toxin molecule can be used to estimate dimensions of the potassium channel. Surface-exposed residues, Arg24, Lys27, and Arg31 of the beta-sheet, have been identified from mutagenesis studies as functionally important for blocking the Shaker K+ channel. The sequential and spatial locations of Arg24 and Arg31 are not conserved among the homologous toxins. Knowledge on the details of the channel-binding sites of agitoxin 2 formed a basis for site-directed mutagenesis studies of the toxin and the K+ channel sequences. Observed interactions between mutated toxin and channel are being used to elucidate the channel structure and mechanisms of channel-toxin interactions. 相似文献
22.
The incorporation of [14C] N-ethylmaleimide reveals fast and slow-reacting sulfhydryl groups in sarcoplasmic reticulum. Two proteins react with the label: a fast-reacting glycoprotein recently isolated (Ikemoto, Cucchiaro and Garcia (1976) J. Cell Biol., 290a), and the Ca2+-ATPase. Labeling sarcoplasmic reticulum with a maleimide spin label gives a similar pattern. The spectra of maleimide-spin-labeled sarcoplasmic reticulum have both ‘strongly’ and ‘weakly’ immobilized components. Maleimide-spin-labeled purified Ca2+-ATPase, or sarcoplasmic reticulum labeled first with N-ethylmaleimide, and then with maleimide spin label, show spectra devoid of the ‘weakly’ immobilized component; the latter is enhanced in partially purified glycoprotein obtained from spin-labeled sarcoplasmic reticulum. This indicates that spectra from maleimide-spin-labeled sarcoplasmic reticulum do not reflect exclusively the state of the Ca2+-ATPase enzyme. 相似文献
23.
The effect of mexiletine on oxygen and glucose consumption was studied both in homogenate and slices of brain, liver and myocardium of Wistar rats. Oxygen consumption was detected by means of Warburg's manometric techniques, and glucose utilization by the enzymatic method of glucose oxidase. Whilst glucose uptake was not modified in any of the studied preparations, mexiletine promoted a significant increase of oxygen consumption in the homogenized slices, and an inhibition in the intact tissue. 相似文献
24.
25.
Inositol 1,4,5-triphosphate phosphatase activity in membranes isolated from amphibian skeletal muscle [corrected 总被引:1,自引:0,他引:1
The hydrolysis of [3H]inositol 1,4,5-trisphosphate by a soluble fraction and by isolated transverse tubule and sarcoplasmic reticulum membranes from frog skeletal muscle was studied. Transverse tubule membranes displayed rates of hydrolysis several-fold higher than those of sacroplasmic reticulum and soluble fraction; Km and Vmax were 25.2 microM and 44.1 nmol/mg/min, respectively. Transverse tubule membranes sequentially hydrolyzed inositol trisphosphate to inositol bisphosphate, inositol 1-phosphate and inositol, indicating that these membranes have inositol bis- and monophosphatases in addition to inositol trisphosphatase. 相似文献
26.
Oxygen regulation of L-1,2-propanediol oxidoreductase activity in Escherichia coli. 总被引:2,自引:2,他引:0 下载免费PDF全文
E Cabiscol E Hidalgo J Badía L Baldom J Ros J Aguilar 《Journal of bacteriology》1990,172(9):5514-5515
Regardless of the respiratory conditions of the culture, Escherichia coli synthesizes an active propanediol oxidoreductase. Under anaerobic conditions, the enzyme remained fully active and accomplished its physiological role, while under aerobic conditions, it was inactivated in a process that did not depend on protein synthesis or on the presence of a carbon source. 相似文献
27.
Haemoprotein degradation and lipid peroxidation were evaluated in rat liver, kidney and heart slices incubated for 2 h in the presence and absence of bromotrichloromethane, antioxidants and chelators to obtain information about the relationship between oxidants and damage to haemoproteins. Haemoproteins were modified by bromotrichloromethane, and this modification, measured as loss of ferrohaemoproteins, generally was concurrent with lipid peroxidation measured as thiobarbituric acid-reactive substances. These two processes occurred simultaneously as a function of incubation time and oxidant concentration. Inhibition of the two processes by nordihydroguaiaretic acid, butylated hydroxyanisole and Trolox C, and lack of inhibition by mannitol, catalase and superoxide dismutase also were coincident. However, Methylene blue, EDTA, sodium fluoride, 2,4-dinitrophenol, N-ethylmaleimide and o-phenanthroline affected the two processes differently. The results suggested that haemoproteins may compete with other molecules for oxidant radicals, thus serving as protectors of cells against oxidant radicals. Products of haemoprotein degradation such as protein polymers, free amino acids and bilirubin may be indicators of in vivo oxidative stress. 相似文献
28.
The transport of taurocholic acid (TA) across Caco-2 cell monolayers was dependent on time in culture and reached a plateau after 28 days, at which time the apical (AP)-to-basolateral (BL) transport was 10-times greater than BL-to-AP transport. The amounts of TA inside the cells following application of 10 nM [14C]TA to the AP or BL side of the monolayers (30 min) were approximately equal (54.4 +/- 2.7 and 64.6 +/- 2.8 fmol/mg protein, respectively). AP-to-BL transport of TA was saturable and temperature-dependent. Vmax and Km for transport were 13.7 pmol/mg protein per min and 49.7 microM, respectively. The transport of TA had an activation energy of 13.2 kcal.mol-1, required Na+ and glucose. AP-to-BL transport of [14C]TA was inhibited by the co-administration (on the AP side) of either unlabeled TA or deoxycholate, but it was not reduced by the presence of unlabeled TA on the BL side. 相似文献
29.
Proteolysis and lipid peroxidation were evaluated in rat liver slices incubated in the presence of the oxidant bromotrichloromethane and effectors of proteolysis. Proteolysis was evaluated by S-amino acids and lipid peroxidation by thiobarbituric acid-reactive substances (TBARS) released into the incubation medium. The increased release of S-amino acids by BrCl3C depended on incubation time and oxidant concentration. S-Amino acid release increased 30% over control value and TBARS increased from 22 to 124 nmol/g liver by incubation for 120 min with 1 mM BrCl3C. Release of S-amino acids and TBARS was decreased when liver slices were treated with nor-dihydroguaiaretic acid (NDG), butylated hydroxyanisole (BHA), Trolox C, or N,N'-diphenyl-1,4-phenylenediamine (DPPD) immediately prior to addition of oxidant, suggesting participation of lipid-soluble free radicals. Oxidant-induced release of S-amino acids but not of TBARS was decreased by mannitol, suggesting participation of hydroxyl radical or a species with similar reactivity; and by superoxide dismutase and catalase, suggesting participation of superoxide and hydrogen peroxide, respectively. The decrease of S-amino acid release by sodium fluoride, sodium arsenate, 2,4-dinitrophenol, chloroquine, leupeptin, phenylmethylsulfonyl fluoride, EDTA and o-phenanthroline was variable, suggesting the presence in liver of several proteases to remove oxidatively-modified proteins. 相似文献
30.
Endogeneous levels of zinc and copper were found to be 1.2±0.1×10−2 and 0.3±0.1×10−2 μg/A260 unit, respectively, in polysomal fractions from control animals; cadmium, however, was undetectable. In experimental
animals (injected with cadmium) zinc, copper, and cadmium were found in polysomal fractions isolated by two different methods.
One hour after a cadmium injection there was a rise in both the zinc and copper content of the polysomal fractions, which
then declined steadily to below control levels by 16 h. Neither zinc nor cadmium were dialyzable from these fractions by a
TRIS buffer; however, addition of 0.01M EDTA to the buffer resulted in removal of 75% of the zinc and all of the detectable cadmium.
The addition of cadmium (CdCl2) to control supernatants (adjusted to the cadmium concentration present in supernatants 6 h after in vivo exposure) resulted
in metal binding to polysomal fractions in levels comparable to those observed after in vivo exposures to the metal. When
cadmium was added in the form of cadmium thionein, a smaller fraction of the metal was isolated with the polysomal fraction.
Cadmium bound to polysomal fractions in vivo (24 h after exposure) was sensitive to release by protease digestion, but insensitive
to release by ribonuclease digestion. 相似文献