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141.
142.
Hersleth HP Uchida T Røhr AK Teschner T Schünemann V Kitagawa T Trautwein AX Görbitz CH Andersson KK 《The Journal of biological chemistry》2007,282(32):23372-23386
High resolution crystal structures of myoglobin in the pH range 5.2-8.7 have been used as models for the peroxide-derived compound II intermediates in heme peroxidases and oxygenases. The observed Fe-O bond length (1.86-1.90 A) is consistent with that of a single bond. The compound II state of myoglobin in crystals was controlled by single-crystal microspectrophotometry before and after synchrotron data collection. We observe some radiation-induced changes in both compound II (resulting in intermediate H) and in the resting ferric state of myoglobin. These radiation-induced states are quite unstable, and compound II and ferric myoglobin are immediately regenerated through a short heating above the glass transition temperature (<1 s) of the crystals. It is unclear how this influences our compound II structures compared with the unaffected compound II, but some crystallographic data suggest that the influence on the Fe-O bond distance is minimal. Based on our crystallographic and spectroscopic data we suggest that for myoglobin the compound II intermediate consists of an Fe(IV)-O species with a single bond. The presence of Fe(IV) is indicated by a small isomer shift of delta = 0.07 mm/s from M?ssbauer spectroscopy. Earlier quantum refinements (crystallographic refinement where the molecular-mechanics potential is replaced by a quantum chemical calculation) and density functional theory calculations suggest that this intermediate H species is protonated. 相似文献
143.
Villard V Agak GW Frank G Jafarshad A Servis C Nébié I Sirima SB Felger I Arevalo-Herrera M Herrera S Heitz F Bäcker V Druilhe P Kajava AV Corradin G 《PloS one》2007,2(7):e645
To identify malaria antigens for vaccine development, we selected alpha-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. The corresponding synthetic peptides are expected to mimic structurally "native" epitopes. Indeed the 95 chemically synthesized peptides were all specifically recognized by human immune sera, though at various prevalence. Peptide specific antibodies were obtained both by affinity-purification from malaria immune sera and by immunization of mice. These antibodies did not show significant cross reactions, i.e., they were specific for the original peptide, reacted with native parasite proteins in infected erythrocytes and several were active in inhibiting in vitro parasite growth. Circular dichroism studies indicated that the selected peptides assumed partial or high alpha-helical content. Thus, we demonstrate that the bioinformatics/chemical synthesis approach described here can lead to the rapid identification of molecules which target biologically active antibodies, thus identifying suitable vaccine candidates. This strategy can be, in principle, extended to vaccine discovery in a wide range of other pathogens. 相似文献
144.
Previous preparations of the Na(+) F(1)F(0)-ATP synthase solubilized by Triton X-100 lacked some of the membrane-embedded motor subunits [Reidlinger J & Müller V (1994) Eur J Biochem233, 275-283]. To improve the subunit recovery, we revised our purification protocol. The ATP synthase was solubilized with dodecylmaltoside and further purified to apparent homogeneity by chromatographic techniques. The preparation contained, along with the F(1) subunits, the entire membrane-embedded motor with the stator subunits a and b, and the heterooligomeric c ring, which contained the V(1)V(0)-like subunit c(1) and the F(1)F(0)-like subunits c(2) and c(3). After incorporation into liposomes, ATP synthesis could be driven by an electrochemical sodium ion potential or a potassium ion diffusion potential, but not by a sodium ion potential. This is the first demonstration that an ATPase with a V(0)-F(0) hybrid motor is capable of ATP synthesis. 相似文献
145.
Züst R Cervantes-Barragán L Kuri T Blakqori G Weber F Ludewig B Thiel V 《PLoS pathogens》2007,3(8):e109
Attenuated viral vaccines can be generated by targeting essential pathogenicity factors. We report here the rational design of an attenuated recombinant coronavirus vaccine based on a deletion in the coding sequence of the non-structural protein 1 (nsp1). In cell culture, nsp1 of mouse hepatitis virus (MHV), like its SARS-coronavirus homolog, strongly reduced cellular gene expression. The effect of nsp1 on MHV replication in vitro and in vivo was analyzed using a recombinant MHV encoding a deletion in the nsp1-coding sequence. The recombinant MHV nsp1 mutant grew normally in tissue culture, but was severely attenuated in vivo. Replication and spread of the nsp1 mutant virus was restored almost to wild-type levels in type I interferon (IFN) receptor-deficient mice, indicating that nsp1 interferes efficiently with the type I IFN system. Importantly, replication of nsp1 mutant virus in professional antigen-presenting cells such as conventional dendritic cells and macrophages, and induction of type I IFN in plasmacytoid dendritic cells, was not impaired. Furthermore, even low doses of nsp1 mutant MHV elicited potent cytotoxic T cell responses and protected mice against homologous and heterologous virus challenge. Taken together, the presented attenuation strategy provides a paradigm for the development of highly efficient coronavirus vaccines. 相似文献
146.
Forest health status in Europe is assessed by the International Cooperative Programme on Assessment and Monitoring of Air Pollution Effects on Forests (ICP Forests). Established by the Convention on Long-Range Transboundary Air Pollution (CLRTAP) under the United Nations Economic Commission for Europe (UNECE), the ICP Forests has been monitoring forest condition in close cooperation with the European Commission (EC) for 20 years. The present paper describes the latest results of the deposition measurements on permanent monitoring plots and of the extensive defoliation sample survey. The findings reveal marked spatial patterns in bulk and throughfall depositions of nitrate (N-NO3(-)), ammonium (N-NH4(+)), and sulfate (S-SO4(2-)), as well as an obvious decrease in bulk and throughfall deposition of sulfate. Latest analyses of defoliation data confirm previous results, indicating a high correlation with weather extremes. 相似文献
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International Microbiology - The methylene-tetrahydrofolate reductase (MTHFR) is a key enzyme in acetogenic CO2 fixation. The MetVF-type enzyme has been purified from four different species and the... 相似文献
150.
Lara A Gruijs da Silva Francesca Simonetti Saskia Hutten Henrick Riemenschneider Erin L Sternburg Lisa M Pietrek Jakob Gebel Volker Dtsch Dieter Edbauer Gerhard Hummer Lukas S Stelzl Dorothee Dormann 《The EMBO journal》2022,41(8)
Post‐translational modifications (PTMs) have emerged as key modulators of protein phase separation and have been linked to protein aggregation in neurodegenerative disorders. The major aggregating protein in amyotrophic lateral sclerosis and frontotemporal dementia, the RNA‐binding protein TAR DNA‐binding protein (TDP‐43), is hyperphosphorylated in disease on several C‐terminal serine residues, a process generally believed to promote TDP‐43 aggregation. Here, we however find that Casein kinase 1δ‐mediated TDP‐43 hyperphosphorylation or C‐terminal phosphomimetic mutations reduce TDP‐43 phase separation and aggregation, and instead render TDP‐43 condensates more liquid‐like and dynamic. Multi‐scale molecular dynamics simulations reveal reduced homotypic interactions of TDP‐43 low‐complexity domains through enhanced solvation of phosphomimetic residues. Cellular experiments show that phosphomimetic substitutions do not affect nuclear import or RNA regulatory functions of TDP‐43, but suppress accumulation of TDP‐43 in membrane‐less organelles and promote its solubility in neurons. We speculate that TDP‐43 hyperphosphorylation may be a protective cellular response to counteract TDP‐43 aggregation. 相似文献