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151.
High-throughput approaches are beginning to have an impact on many areas of yeast biology. Two recent studies, using different experimental platforms, provide insight into new pathways involved in the response of yeast to DNA damage. 相似文献
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Beetz C Brodhun M Moutzouris K Kiehntopf M Berndt A Lehnert D Deufel T Bastmeyer M Schickel J 《Biochemical and biophysical research communications》2004,318(4):1079-1084
Mutations in the human spastin gene (SPG4) cause the most prevalent form of autosomal dominant hereditary spastic paraplegia (HSP), a neurodegenerative disorder characterised by progressive weakness and spasticity of the lower limbs. We address the question of intracellular localisation of spastin. Using polyclonal antibodies against N-terminal spastin sequences, we find that the native protein is localised in both the perinuclear cytoplasm and the nucleus. To identify structural motifs within the protein that can explain entry into the nucleus, we developed a reporter system to test nuclear localisation sequence (NLS)-functionality based on four in-frame fused copies of green fluorescent protein. Using this novel tool we demonstrate that spastin carries two NLSs located in exons 1 and 6. Both are independently functional in mediating nuclear entry. 相似文献
155.
The objective of this article is to reappraise previous published data on the mortality of male shift workers from Taylor and Pocock (1972). Mortality rate ratios were calculated for shift workers, ex-shift workers, and for shift workers plus ex-shift workers, respectively, compared to day workers using the Mantel-Haenszel method. The overall risk for current and former shift workers was 1.05 (95% Confidence Interval: 0.95-1.16). For ex-shift workers the mortality was increased compared to day workers (1.24, 95% Confidence Interval: 1.03-1.51). In the age specific analyses increased mortality was observed in shift workers compared with day workers in the age group of 45-54 yrs (Relative Risk: 1.47, 95% Confidence Interval: 1.12-1.93). We suggest that shift work is associated with increased mortality risk. 相似文献
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Andrews RK Gardiner EE Shen Y Whisstock JC Berndt MC 《The international journal of biochemistry & cell biology》2003,35(8):1170-1174
Glycoprotein (GP) Ib-IX-V is a remarkable platelet adhesion receptor of the leucine-rich repeat family. It has evolved to fulfil its major function of initiating platelet aggregation (thrombus formation) at high-shear stress in flowing blood. In addition to binding von Willebrand factor (vWF) in subendothelial matrix or plasma to trigger platelet aggregation, GPIb-IX-V also binds counter-receptors, alphaMbeta2 (Mac-1) on neutrophils or P-selectin on activated platelets or endothelial cells. GPIb-IX-V ligands also include alpha-thrombin, clotting factors XI/XIIa, and high-molecular-weight kininogen. Interactions involving GPIb-IX-V are therefore central to vascular processes of thrombosis and inflammation, and the receptor is under intense scrutiny as a potential therapeutic target. 相似文献
159.
Human spermatid-specific thioredoxin-1 (Sptrx-1) is a two-domain protein with oxidizing activity 总被引:1,自引:0,他引:1
Jiménez A Johansson C Ljung J Sagemark J Berndt KD Ren B Tibbelin G Ladenstein R Kieselbach T Holmgren A Gustafsson JA Miranda-Vizuete A 《FEBS letters》2002,530(1-3):79-84
Spermatid-specific thioredoxin-1 (Sptrx-1) is the first member of the thioredoxin family of proteins with a tissue-specific expression pattern, found exclusively in the tail of elongating spermatids and spermatozoa. We describe here further biochemical characterization of human Sptrx-1 protein structure and enzymatic activity. In gel filtration chromatography human Sptrx-1 eluates as a 400 kDa protein consistent with either an oligomeric form, not maintained by intermolecular disulfide bonding, and/or a highly asymmetrical structure. Analysis of circular dichroism spectra of fragments 1–360 and 361–469 and comparison to spectra of full-length Sptrx-1 supports a two-domain organization with a largely unstructured N-terminal domain and a folded thioredoxin-like C-terminal domain. Functionally, Sptrx-1 behaves as an oxidant in vitro when using selenite, but not oxidized glutathione, as electron acceptor. This oxidizing enzymatic activity suggests that Sptrx-1 might govern the stabilization (by disulfide cross-linking) of the different structures in the developing tail of spermatids and spermatozoa. 相似文献
160.
Benach J Filling C Oppermann UC Roversi P Bricogne G Berndt KD Jörnvall H Ladenstein R 《Biochemistry》2002,41(50):14659-14668
The enzyme 3beta/17beta-hydroxysteroid dehydrogenase (3beta/17beta-HSD) is a steroid-inducible component of the Gram-negative bacterium Comamonas testosteroni. It catalyzes the reversible reduction/dehydrogenation of the oxo/beta-hydroxy groups at positions 3 and 17 of steroid compounds, including hormones and isobile acids. Crystallographic analysis at 1.2 A resolution reveals the enzyme to have nearly identical subunits that form a tetramer with 222 symmetry. This is one of the largest oligomeric structures refined at this resolution. The subunit consists of a monomer with a single-domain structure built around a seven-stranded beta-sheet flanked by six alpha-helices. The active site contains a Ser-Tyr-Lys triad, typical for short-chain dehydrogenases/reductases (SDR). Despite their highly diverse substrate specificities, SDR members show a close to identical folding pattern architectures and a common catalytic mechanism. In contrast to other SDR apostructures determined, the substrate binding loop is well-defined. Analysis of structure-activity relationships of catalytic cleft residues, docking analysis of substrates and inhibitors, and accessible surface analysis explains how 3beta/17beta-HSD accommodates steroid substrates of different conformations. 相似文献