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221.
222.
Lev-Goldman V Mester B Ben-Aroya N Hanoch T Rupp B Stanoeva T Gescheidt G Seger R Koch Y Weiner L Fridkin M 《Bioorganic & medicinal chemistry》2008,16(14):6789-6798
We synthesized two carminic acid (7-alpha-d-glucopyranosyl-9,10-dihydro-3,5,6,8-tetrahydroxy-1-methyl-9,10-dioxo-2-anthracene carboxlic acid, CA)-GnRH conjugates to be used as a model for potential photoactive targeted compounds. CA was conjugated to the epsilon-amino group of [d-Lys(6)]GnRH through its carboxylic moiety or via a beta-alanine spacer (beta-ala). Redox potentials of CA and its conjugates were determined. We used electron spin resonance (ESR) and spin trapping techniques to study the light-stimulated redox properties of CA and its CA-GnRH conjugates. Upon irradiation, the compounds stimulated the formation of reactive oxygen species (ROS), that is, singlet oxygen ((1)O(2)) and oxygen radicals (O(2)(-*) and OH(*)). Both conjugates exhibited higher ROS production than the non-conjugated CA. The bioactivity properties of the CA conjugates and the parent peptide, [d-Lys(6)]GnRH, were tested on primary rat pituitary cells. We found that the conjugates preserved the bioactivity of GnRH as illustrated by their capability to induce ERK phosphorylation and LH release. 相似文献
223.
Isolation of intrinsically active (MEK-independent) variants of the ERK family of mitogen-activated protein (MAP) kinases 总被引:1,自引:0,他引:1
Levin-Salomon V Kogan K Ahn NG Livnah O Engelberg D 《The Journal of biological chemistry》2008,283(50):34500-34510
MAPKs are key components of cell signaling pathways with a unique activation mechanism: i.e. dual phosphorylation of neighboring threonine and tyrosine residues. The ERK enzymes form a subfamily of MAPKs involved in proliferation, differentiation, development, learning, and memory. The exact role of each Erk molecule in these processes is not clear. An efficient strategy for addressing this question is to activate individually each molecule, for example, by expressing intrinsically active variants of them. However, such molecules were not produced so far. Here, we report on the isolation, via a specifically designed genetic screen, of six variants (each carries a point mutation) of the yeast MAPK Mpk1/Erk that are active, independent of upstream phosphorylation. One of the activating mutations, R68S, occurred in a residue conserved in the mammalian Erk1 (Arg-84) and Erk2 (Arg-65) and in the Drosophila ERK Rolled (Arg-80). Replacing this conserved Arg with Ser rendered these MAPKs intrinsically active to very high levels when tested in vitro as recombinant proteins. Combination of the Arg to Ser mutation with the sevenmaker mutation (producing Erk2(R65S+D319N) and Rolled(R80S+D334N)) resulted in even higher activity (45 and 70%, respectively, in reference to fully active dually phosphorylated Erk2 or Rolled). Erk2(R65S) and Erk2(R65S+D319N) were found to be spontaneously active also when expressed in human HEK293 cells. We further revealed the mechanism of action of the mutants and show that it involves acquisition of autophosphorylation activity. Thus, a first generation of Erk molecules that are spontaneously active in vitro and in vivo has been obtained. 相似文献
224.
Although protein secretion occurs post-translationally in bacteria and is mainly a cotranslational event in Eukarya, the relationship between the translation and translocation of secreted proteins in Archaea is not known. To address this question, the signal peptide-encoding region of the surface layer glycoprotein gene from the Haloarchaea Haloferax volcanii was fused either to the cellulose-binding domain of the Clostridium thermocellum cellulosome or to the cytoplasmic enzyme dihydrofolate reductase from H. volcanii. Signal peptide-cleaved mature versions of both the cellulose-binding domain and dihydrofolate reductase could be detected in the growth medium of transformed H. volcanii cells. Immunoblot analysis revealed, however, the presence of full-length signal peptide-bearing forms of both proteins inside the cytoplasm of the transformed cells. Proteinase accessibility assays confirmed that the presence of cell-associated signal peptide-bearing proteins was not due to medium contamination. Moreover, the pulse-radiolabeled signal peptide cellulose-binding domain chimera could be chased from the cytoplasm into the growth medium even following treatment with anisomycin, an antibiotic inhibitor of haloarchaeal protein translation. Thus, these results provide evidence that, in Archaea, at least some secreted proteins are first synthesized inside the cell and only then translocated across the plasma membrane into the medium. 相似文献
225.
Irihimovitch V Ring G Elkayam T Konrad Z Eichler J 《Extremophiles : life under extreme conditions》2003,7(1):71-77
By exploiting the salt-insensitive interaction of the cellulose-binding domain (CBD) of the Clostridium thermocellum cellulosome with cellulose, purification of CBD-fused versions of SecY and SecE, components of the translocation apparatus of the halophilic archaeon Haloferax volcanii, was undertaken. Following transformation of Haloferax volcanii cells with CBD-SecY- or -SecE-encoding plasmids, cellulose-based purification led to the capture of stably expressed, membrane-bound 68 and 25 kDa proteins, respectively. Both fusion proteins were recognized by antibodies raised against the CBD. Thus, CBD-cellulose interactions can be employed as a salt-insensitive affinity purification system for the capture of complexes containing the Haloferax volcanii translocation apparatus components SecY and SecE. 相似文献
226.
Propionibacterium thoenii P-127 produces and releases to the growth medium antibacterial agents that can be used as natural preservatives. The concentrations of these antibacterial agents in the growth medium are very low, and their activity can be detected only in concentrated medium, even in a bioreactor. A simple and efficient system to produce propionicin PLG-1 without the use of a bioreactor was investigated. Fermentation in screw-cap bottles without shaking produced antibacterial activity similar to that of fermentation in plates, but in a shorter time. Sodium lactate medium (NaLa) was found to be the most supportive for PLG-1 production compared to lactic acid bacteria media such as M-17 or beet molasses/corn. The initial concentration of the carbon source, sodium lactate, agar concentration, and the initial pH of the medium affected the synthesis of PLG-1. Additions of NaCl up to 1% showed no effect on the antibacterial agent production. The optimal conditions for production of the antibacterial agent were fermentation for 9 days in screw-cap bottles in modified NaLa medium (M-NaLa) containing 1% yeast extract, 1% tryptic soy broth, 0.9% lactic acid, and 0.6% agar, adjusted to pH of 9. 相似文献
227.
Eshed V Gopher A Galili E Hershkovitz I 《American journal of physical anthropology》2004,123(4):303-315
This paper attempts to quantify the changes in activity patterns of early farming populations in the Levant through the musculoskeletal stress markers (MSM) of the upper limb as seen in skeletal remains. The transition to an agricultural way of life resulted in higher loads on the upper limb in Neolithic populations compared to the Natufian hunter-gatherer populations that preceded them. The MSM pattern for males and females indicates a gender-based division of labor both in the Natufian and the Neolithic. It may also suggest that people in the Neolithic period were engaged in different (new) activities and occupations compared to the Natufian. 相似文献
228.
Yosef I Irihimovitch V Knopf JA Cohen I Orr-Dahan I Nahum E Keasar C Shapira M 《The Journal of biological chemistry》2004,279(11):10148-10156
Transfer of the green algae Chlamydomonas reinhardtii from low light to high light generated an oxidative stress that led to a dramatic arrest in the synthesis of the large subunit (LSU) of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). The translational arrest correlated with transient changes in the intracellular levels of reactive oxygen species and with shifting the glutathione pool toward its oxidized form (Irihimovitch, V., and Shapira, M. (2000) J. Biol. Chem. 275, 16289-16295). Here we examined how the redox potential of glutathione affected the RNA-protein interactions with the 5'-untranslated region of rbcL. This RNA region specifically binds a group of proteins with molecular masses of 81, 62, 51, and 47 kDa in UV-cross-linking experiments under reducing conditions. Binding of these proteins was interrupted by exposure to oxidizing conditions (GSSG), and a new protein of 55 kDa was shown to interact with the RNA. The 55-kDa protein comigrated with Rubisco LSU in one- and two-dimensional gels, and its RNA binding activity was further verified by using the purified protein in UV-cross-linking experiments under oxidizing conditions. However, the LSU of purified and oxidized Rubisco bound to RNA in a sequence-independent manner. A remarkable structural similarity was found between the amino-terminal domain of Rubisco LSU in C. reinhardtii and the RNA binding domain, a highly prevailing motif among RNA-binding proteins. It appears from the crystal structure of Rubisco that the amino terminus of LSU is buried within the holoenzyme. We propose that under oxidizing conditions it is exposed to the surface and can, therefore, bind RNA. Accordingly, a recombinant form of the polypeptide domain that corresponds to the amino terminus of LSU was found to bind RNA in vitro with or without GSSG. 相似文献
229.
Wolk M Valinsky L Sompolinsky D Sechter I Schmidt H Tetry S Agmon V 《FEMS microbiology letters》2004,239(2):249-254
During a period of four years, multidrug-resistant Escherichia coli of particular serotypes have been isolated from 255 elderly (>65 years) patients from four hospitals in central Israel. 83% of the isolates belonged to one of four predominant serotypes (O153:H31, O101:H-, O2:H42, and O102:H6). All isolates were producers of extended spectrum beta-lactamases and resistant to ciprofloxacin. To our knowledge, the involved serotypes have hitherto not been reported as etiological agents of extraintestinal human infections (MEDLINE). Pulsed-field gel electrophoresis of isolates from one of the most frequent serotypes indicated a clonal relationship between them. Further investigation of these strains and analysis of their virulence factors may help to confine their spread. 相似文献
230.