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Crystal structure analysis of an A-DNA fragment at 1.8 A resolution: d(GCCCGGGC). 总被引:12,自引:9,他引:3 下载免费PDF全文
Single crystals of the self-complementary octadeoxyribonucleotide d(GCCCGGGC) have been analysed by X-ray diffraction methods at a resolution of 1.8 A. The tetragonal unit cell of space group P4(3)2(1)2 has dimensions of a = 43.25 A and c = 24.61 A and contains eight strands of the oligonucleotide. The structure was refined by standard crystallographic techniques to an R factor of 17.1% using 1359 3 sigma structure factor observations. Two strands of the oligonucleotide are related by the crystallographic dyad axis to form a DNA helix in the A conformation. The d(GCCCGGGC) helix is characterized by a wide open major groove, a near perpendicular orientation of base pairs to the helix axis and an unusually small average helix twist angle of 31.3 degrees indicating a slightly underwound helix with 11.5 base pairs per turn. Extensive cross-strand stacking between guanine bases at the central cytosine-guanine step is made possible by a number of local conformational adjustments including a fully extended sugar-phosphate backbone of the central guanosine nucleotide. 相似文献
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Fast synaptic transmission in the vertebrate brain is mediated by ligand-gated channel receptors. As some of these receptors have been implicated in learning and memory, it is important to understand their mechanism of action at a molecular level. Excitatory receptors are members of large gene families of related channels that are gated by acetylcholine, serotonin, and the most abundant neurotransmitter, glutamate. Within the last year, a number of important studies have focused on the ability of these channels to flux calcium ions. Calcium entry into neurons through some of these channels triggers biochemical cascades, which can lead to changes in synaptic efficacy, presumed to be a requisite for memory formation, or if it occurs in excess, to cell death. Recent studies that attempt to determine the channel structures responsible for this calcium conductance will be discussed. 相似文献
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Step reductions in extracellular Ca2+ activate a transient inward current in chick dorsal root ganglion cells. 下载免费PDF全文
We investigated whether transient step reductions in divalent cations would produce detectable changes in neuronal excitability similar to those reported in the total absence of divalent cations. Using cultured chick dorsal root ganglion cells as a model system, our results indicate that a step reduction in divalent cations induces a transient inward current. This response is mediated by a tetrodotoxin-resistant, Na+-permeable, cation channel that is blocked by cadmium. This, and our observation that the response is abolished by verapamil, suggests that the current passes through calcium channels. This transient inward current was estimated to be activated by decreases in extracellular calcium ([Ca2+]o) as small as 0.5-0.8 mM and thus represents a different response from the one previously observed when steady-state [Ca2+]o levels were reduced to micromolar levels. 相似文献
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J Ozols G Korza F S Heinemann M A Hediger P Strittmatter 《The Journal of biological chemistry》1985,260(22):11953-11961
The complete covalent structure of liver microsomal NADH-cytochrome b5 reductase from steer liver microsomes was determined. Cleavage at methionyl bonds gave 10 peptides accounting for all the residues of the protein. Acid cleavage of the reductase at the Asp-Pro bonds gave three peptides accounting for all the CNBr peptides in the molecule. Subfragmentation of these peptides by chemical and enzymatic cleavage provided overlaps which established all the fragments in an unambiguous sequence of 300 residues, corresponding to Mr 34,110. Limited tryptic digestion cleaved reductase at residues 28 and 119, yielding a preparation having two noncovalently linked peptides having a conformation which binds flavin and retains the structural features essential for NADH-cytochrome b5 activity. A model for the secondary structure of cytochrome b5 reductase is proposed that is based on computer-assisted analysis of the amino acid sequence. In this model the beta-turns are predominant and there is some 25% alpha and 30% beta structure. 相似文献
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Induction of Lambda-Bacteriophage in Escherichia coli as a Screening Test for Potential Antitumor Agents 总被引:6,自引:5,他引:1 下载免费PDF全文
A simple, rapid, quantitative test procedure to measure induction of phage production in lysogenic Escherichia coli K-12 (λ) was described. This test was used in a study of 209 substances, including antibiotics, pyrimirines, purines, alkylating agents, thiols, amino acids, vitamins, and miscellaneous compounds. Minimal inducing concentrations for the 26 (12.5% of total tested) substances found to be effective inducing agents, as well as a listing of the inactive compounds, are presented. Since 21 of the 26 active agents reportedly have antineoplastic activity in rodent tumor systems, it was concluded that the induction test may provide a useful screen for the detection of potentially useful antitumor compounds. 相似文献
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Uwe Ludewig Christoph Lorra Olaf Pongs Stefan H. Heinemann 《European biophysics journal : EBJ》1993,22(4):237-247
The members of the RCK family of cloned voltage-dependent K+ channels are quite homologous in primary structure, but they are highly diverse in functional properties. RCK4 channels differ from RCK1 and RCK2 channels in inactivation and permeation properties, the sensitivity to external TEA, and to current modulation by external K+ ions. Here we show several other interesting differences: While RCK1 and RCK2 are blocked in a voltage and concentration dependent manner by internal Mg2+ ions, RCK4 is only weakly blocked at very high potentials. The single-channel current-voltage relations of RCK4 are rather linear while RCK2 exhibits an inwardly rectifying single-channel current in symmetrical K+ solutions. The deactivation of the channels, measured by tail current protocols, is faster in RCK4 by a factor of two compared with RCK2. In a search for the structural motif responsible for these differences, point mutants creating homology between RCK2 and RCK4 in the pore region were tested. The single-point mutant K533Y in the background of RCK4 conferred the properties of Mg2+ block, tail current kinetics, and inward ion permeation of RCK2 to RCK4. This mutant was previously shown to be responsible for the alterations in external TEA sensitivity and channel regulation by external K+ ions. Thus, this residue is expected to be located at the external side of the pore entrance. The data are consistent with the idea that the mutation alters the channel occupancy by K+ and thereby indirectly affects internal Mg2+ block and channel closing.Abbreviations TEA
tetraethylammonium
- EGTA
Ethylene glycol-bis (-aminoethyl ether) N,N,N,N-tetraacetic acid
- 2S3B model
2-site 3-barrier model
Correspondence to: S. H. Heinemann 相似文献
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L. A. Heinemann M. A. Lewis M. Thorogood W. O. Spitzer I. Guggenmoos-Holzmann R. Bruppacher 《BMJ (Clinical research ed.)》1997,315(7121):1502-1504