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811.
Toogood HS van Thiel A Scrutton NS Leys D 《The Journal of biological chemistry》2005,280(34):30361-30366
Crystal structures of protein complexes with electron-transferring flavoprotein (ETF) have revealed a dual protein-protein interface with one region serving as anchor while the ETF FAD domain samples available space within the complex. We show that mutation of the conserved Glu-165beta in human ETF leads to drastically modulated rates of interprotein electron transfer with both medium chain acyl-CoA dehydrogenase and dimethylglycine dehydrogenase. The crystal structure of free E165betaA ETF is essentially identical to that of wild-type ETF, but the crystal structure of the E165betaA ETF.medium chain acyl-CoA dehydrogenase complex reveals clear electron density for the FAD domain in a position optimal for fast interprotein electron transfer. Based on our observations, we present a dynamic multistate model for conformational sampling that for the wild-type ETF. medium chain acyl-CoA dehydrogenase complex involves random motion between three distinct positions for the ETF FAD domain. ETF Glu-165beta plays a key role in stabilizing positions incompatible with fast interprotein electron transfer, thus ensuring high rates of complex dissociation. 相似文献
812.
Essential and nonessential elements in the 3' nontranslated region of Bovine viral diarrhea virus 总被引:1,自引:0,他引:1
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The 3' nontranslated region (NTR) of the pestivirus Bovine viral diarrhea virus (BVDV), a close relative of human Hepatitis C virus, consists of three stem-loops which are separated by two single-stranded regions. As in other positive-stranded RNA viruses, the 3' NTR of pestiviruses is involved in crucial processes of the viral life cycle. While several studies characterized cis-acting elements within the 3' NTR of a BVDV replicon, there are no studies addressing the significance of these elements in the context of a replicating virus. To examine the functional importance of 3' NTR elements, a set of 4-base deletions and deletions of each of the three stem-loops were introduced into an infectious BVDV cDNA clone. Emerging mutant viruses were characterized with regard to plaque phenotype, growth kinetics, and synthesis of viral RNA. The results indicated that presence of stem-loop (SL) I and the 3'-terminal part of the single-stranded region between stem-loops I and II are indispensable for pestiviral replication. In contrast, deletions within SL II and SL III as well as absence of either SL II or SL III still allowed efficient viral replication; however, a mutant RNA lacking both SL II and SL III was not infectious. The results of this study provide a detailed map of the essential and nonessential elements within the 3' NTR of BVDV and contribute to our understanding of sequence and structural elements important for efficient viral replication of pestiviruses in natural host cells. 相似文献
813.
Gazzarrini S Severino M Lombardi M Morandi M DiFrancesco D Van Etten JL Thiel G Moroni A 《FEBS letters》2003,552(1):12-16
The chlorella virus PBCV-1 was the first virus found to encode a functional potassium channel protein (Kcv). Kcv is small (94 aa) and basically consists of the M1-P-M2 (membrane-pore-membrane) module typical of the pore regions of all known potassium channels. Kcv forms functional channels in three heterologous systems. This brief review discusses the gating, permeability and modulation properties of Kcv and compares them to the properties of bacterial and mammalian K+ channels. 相似文献
814.
Jin Q van Eynde A Beullens M Roy N Thiel G Stalmans W Bollen M 《The Journal of biological chemistry》2003,278(33):30677-30685
815.
816.
The factors that influence experience-dependent plasticity in the human brain are unknown. We used event-related functional magnetic resonance imaging (fMRI) and a pharmacological manipulation to measure cholinergic modulation of experience-dependent plasticity in human auditory cortex. In a differential aversive conditioning paradigm, subjects were presented with high (1600 Hz) and low tones (400 Hz), one of which was conditioned by pairing with an electrical shock. Prior to presentation, subjects were given either a placebo or an anticholinergic drug (0.4 mg iv scopolamine). Experience-dependent plasticity, expressed as a conditioning-specific enhanced BOLD response, was evident in auditory cortex in the placebo group, but not with scopolamine. This study provides in vivo evidence that experience-dependent plasticity, evident in hemodynamic changes in human auditory cortex, is modulated by acetylcholine. 相似文献
817.
Bacteria were isolated from Mediterranean sponges and specifically selected according to their antimicrobial activity. They were classified on the basis of partial 16S rDNA sequences as members of distinct clusters of alpha-Proteobacteria and gamma-Proteobacteria. The action spectrum of antimicrobial activities against target organisms was related to the phylogenetic position of the isolates. 相似文献
818.
819.
Kevin?WhittingstallEmail author Gerhard?Stroink Larry?Gates JF?Connolly Allen?Finley 《Biomedical engineering online》2003,2(1):14
Background
The electroencephalogram (EEG) reflects the electrical activity in the brain on the surface of scalp. A major challenge in this field is the localization of sources in the brain responsible for eliciting the EEG signal measured at the scalp. In order to estimate the location of these sources, one must correctly model the sources, i.e., dipoles, as well as the volume conductor in which the resulting currents flow. In this study, we investigate the effects of dipole depth and orientation on source localization with varying sets of simulated random noise in 4 realistic head models. 相似文献820.
Deficiency of GDP-Man:GlcNAc2-PP-dolichol mannosyltransferase causes congenital disorder of glycosylation type Ik
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Schwarz M Thiel C Lübbehusen J Dorland B de Koning T von Figura K Lehle L Körner C 《American journal of human genetics》2004,74(3):472-481
The molecular nature of a severe multisystemic disorder with a recurrent nonimmune hydrops fetalis was identified as deficiency of GDP-Man:GlcNAc(2)-PP-dolichol mannosyltransferase, the human orthologue of the yeast ALG1 gene (MIM 605907). The disease belongs to the group of congenital disorders of glycosylation (CDG) and is designated as subtype CDG-Ik. In patient-derived serum, the total amount of the glycoprotein transferrin was reduced. Moreover, a partial loss of N-glycan chains was observed, a characteristic feature of CDG type I forms. Metabolic labeling with [6-(3)H]glucosamine revealed an accumulation of GlcNAc(2)-PP-dolichol and GlcNAc(1)-PP-dolichol in skin fibroblasts of the patient. Incubation of fibroblast extracts with [(14)C]GlcNAc(2)-PP-dolichol and GDP-mannose indicated a severely reduced activity of the beta 1,4-mannosyltransferase, elongating GlcNAc(2)-PP-dolichol to Man(1)GlcNAc(2)-PP-dolichol at the cytosolic side of the endoplasmic reticulum. Genetic analysis of the patient's hALG1 gene identified a homozygous mutation leading to the exchange of a serine residue to leucine at position 258 in the hALG1 protein. The disease-causing nature of the hALG1 mutation for the glycosylation defect was verified by a retroviral complementation approach in patient-derived primary fibroblasts and was confirmed by the expression of wild-type and mutant hALG1 in the Saccharomyces cerevisiae alg1-1 strain. 相似文献