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951.
952.
Ripoll-Rozada J Peña A Rivas S Moro F de la Cruz F Cabezón E Arechaga I 《The Journal of biological chemistry》2012,287(21):17408-17414
TrwD, the VirB11 homologue in conjugative plasmid R388, is a member of the large secretion ATPase superfamily, which includes ATPases from bacterial type II and type IV secretion systems, type IV pilus, and archaeal flagellae assembly. Based on structural studies of the VirB11 homologues in Helicobacter pylori and Brucella suis and the archaeal type II secretion ATPase GspE, a unified mechanism for the secretion ATPase superfamily has been proposed. Here, we have found that the ATP turnover of TrwD is down-regulated by physiological concentrations of magnesium. This regulation is exerted by increasing the affinity for ADP, hence delaying product release. Circular dichroism and limited proteolysis analysis indicate that magnesium induces conformational changes in the protein that promote a more rigid, but less active, form of the enzyme. The results shown here provide new insights into the catalytic mechanism of the secretion ATPase superfamily. 相似文献
953.
Muchova T Quintal SM Farrell NP Brabec V Kasparkova J 《Journal of biological inorganic chemistry》2012,17(2):239-245
When antitumor platinum drugs react with DNA they form various types of intrastrand and interstrand cross-links (CLs). One
class of new antitumor platinum compounds comprises bifunctional PtII compounds based on the dinuclear or trinuclear geometry of leaving ligands. It has been shown that the DNA-binding modes
of dinuclear or trinuclear bifunctional PtII agents are distinct from those of mononuclear cisplatin, forming markedly more intramolecular interstrand CLs. However, at
least two types of DNA interstrand cross-linking by bifunctional PtII complexes can be envisaged, depending on whether the platinum complex coordinates to the bases in one DNA molecule (intramolecular
interstrand CLs) or in two different DNA duplexes (interduplex CLs). We hypothesized that at least some antitumor bifunctional
poly(di/tri)nuclear complexes could fulfill the requirements placed on interduplex DNA cross-linkers. To test this hypothesis
we studied the interduplex cross-linking capability of a representative of antitumor polynuclear agents, namely, dinuclear
PtII complex [{trans-PtCl(NH3)2}2-μ-{trans-(H2N(CH2)6NH2(CH2)2NH2(CH2)6NH2)}]4+ (BBR3535). The investigations were conducted under molecular crowding conditions mimicking environmental conditions in the
cellular nucleus, namely, in medium containing ethanol, which is a commonly used crowding agent. We found with the aid of
native agarose gel electrophoresis that the DNA interduplex cross-linking efficiency of BBR3535 under molecular crowding conditions
was remarkable: the frequency of these CLs was 54%. In contrast, the interduplex cross-linking efficiency of mononuclear cisplatin
or transplatin was markedly lower (approximately 40-fold or 18-fold, respectively). We suggest that the production of interduplex
CLs in addition to other DNA intramolecular adducts may provide polynuclear PtII compounds with a wider spectrum of cytotoxicity. 相似文献
954.
Ramhorst RE Giribaldi L Fraccaroli L Toscano MA Stupirski JC Romero MD Durand ES Rubinstein N Blaschitz A Sedlmayr P Genti-Raimondi S Fainboim L Rabinovich GA 《Glycobiology》2012,22(10):1374-1386
Mechanisms accounting for the protection of the fetal semi-allograft from maternal immune cells remain incompletely understood. In previous studies, we showed that galectin-1 (Gal1), an immunoregulatory glycan-binding protein, hierarchically triggers a cascade of tolerogenic events at the mouse fetomaternal interface. Here, we show that Gal1 confers immune privilege to human trophoblast cells through the modulation of a number of regulatory mechanisms. Gal1 was mainly expressed in invasive extravillous trophoblast cells of human first trimester and term placenta in direct contact with maternal tissue. Expression of Gal1 by the human trophoblast cell line JEG-3 was primarily controlled by progesterone and pro-inflammatory cytokines and impaired T-cell responses by limiting T cell viability, suppressing the secretion of Th1-type cytokines and favoring the expansion of CD4(+)CD25(+)FoxP3(+) regulatory T (T(reg)) cells. Targeted inhibition of Gal1 expression through antibody (Ab)-mediated blockade, addition of the specific disaccharide lactose or retroviral-mediated siRNA strategies prevented these immunoregulatory effects. Consistent with a homeostatic role of endogenous Gal1, patients with recurrent pregnancy loss showed considerably lower levels of circulating Gal1 and had higher frequency of anti-Gal1 auto-Abs in their sera compared with fertile women. Thus, endogenous Gal1 confers immune privilege to human trophoblast cells by triggering a broad tolerogenic program with potential implications in threatened pregnancies. 相似文献
955.
The fermentation of reducing sugars from hardwood (eucalypt) spent sulphite liquor (HSSL) into ethanol by Pichia (Scheffersomyces) stipitis is hindered by concomitant inhibitors of microbial metabolism. The conditions for the HSSL biological treatment step by Paecilomyces variotii were evaluated and optimised. Two different strategies of reactor operation were compared using single batch (B) and sequential batch reactor (SBR). Biological treatment of HSSL in the SBR revealed the best results with respect to the removal of microbial inhibitors. Also, most of inhibitory compounds, acetic acid, gallic acid, pyrogallol, amongst others, were removed from HSSL by P. variotii before the ethanol fermentation. The bio-detoxified HSSL was subjected to a successful fermentation by P. stipitis, attaining a maximum ethanol concentration of 2.4 g L−1 with a yield of 0.24 g ethanol g sugars−1. 相似文献
956.
Monica Olivella Antonio Marchal Manuel Nogueras Adolfo Sánchez Manuel Melguizo Marcela Raimondi Susana Zacchino Fernando Giannini Justo Cobo Ricardo D. Enriz 《Bioorganic & medicinal chemistry》2012,20(20):6109-6122
The design, synthesis, in vitro evaluation, and conformational study of nitrosopyrimidine derivatives acting as antifungal agents are reported. Different compounds structurally related with 4,6-bis(alkyl or arylamino)-5-nitrosopyrimidines were evaluated. Some of these nitrosopyrimidines have displayed a significant antifungal activity against human pathogenic strains. In this paper, we report a new group of nitrosopyrimidines acting as antifungal agents. Among them, compounds 2a, 2b and 15, the latter obtained from a molecular modeling study, exhibited antifungal activity against Candida albicans, Candida tropicalis and Cryptococcus neoformans. We have performed a conformational and electronic analysis on these compounds by using quantum mechanics calculations in conjunction with Molecular Electrostatic Potentials (MEP) obtained from B3LYP/6–31G(d) calculations. Our experimental and theoretical results have led us to identify a topographical template which may provide a guide for the design of new nitrosopyrimidines with antifungal effects. 相似文献
957.
Saúl Martínez-Montero Susana Fernández Yogesh S. Sanghvi Emmanuel A. Theodorakis Mervi A. Detorio Tamara R. Mcbrayer Tony Whitaker Raymond F. Schinazi Vicente Gotor Miguel Ferrero 《Bioorganic & medicinal chemistry》2012,20(23):6885-6893
A series of 2′,3′-dideoxy-2′,2′-difluoro-4′-azanucleosides of both pyrimidine and purine nucleobases were synthesized in an efficient manner starting from commercially available L-pyroglutamic acid via glycosylation of difluorinated pyrrolidine derivative 15. Several 4′-azanucleosides were prepared as a separable mixture of α- and β-anomers. The 6-chloropurine analogue was obtained as a mixture of N7 and N9 regioisomers and their structures were identified based on NOESY and HMBC spectral data. Among the 4′-azanucleosides tested as HIV-1 inhibitors in primary human lymphocytes, four compounds showed modest activity and the 5-fluorouracil analogue (18d) was found to be the most active compound (EC50 = 36.9 μM) in this series. None of the compounds synthesized in this study demonstrated anti-HCV activity. 相似文献
958.
959.
De-Nova JA Medina R Montero JC Weeks A Rosell JA Olson ME Eguiarte LE Magallón S 《The New phytologist》2012,193(1):276-287
? Mesoamerican arid biomes epitomize neotropical rich and complex biodiversity. To document some of the macroevolutionary processes underlying the vast species richness of Mesoamerican seasonally dry tropical forests (SDTFs), and to evaluate specific predictions about the age, geographical structure and niche conservatism of SDTF-centered woody plant lineages, the diversification of Bursera is reconstructed. ? Using a nearly complete Bursera species-level phylogeny from nuclear and plastid genomic markers, we estimate divergence times, test for phylogenetic and temporal diversification heterogeneity, test for geographical structure, and reconstruct habitat shifts. ? Bursera became differentiated in the earliest Eocene, but diversified during independent early Miocene consecutive radiations that took place in SDTFs. The late Miocene average age of Bursera species, the presence of phylogenetic geographical structure, and its strong conservatism to SDTFs conform to expectations derived from South American SDTF-centered lineages. ? The diversification of Bursera suggests that Mesoamerican SDTF richness derives from high speciation from the Miocene onwards uncoupled from habitat shifts, during a period of enhanced aridity resulting mainly from global cooling and regional rain shadows. 相似文献
960.
Eva Vacas Ana M. Bajo Andrew V. Schally Manuel Sánchez-Chapado Juan C. Prieto María J. Carmena 《Peptides》2012
Oxidative stress is a major mediator of tissue and cell injuries. The injury in chronic nephrotic syndrome, acute renal failure, myeloma kidney injury and other kidney diseases is initiated by oxidative stress. We have previously demonstrated that vasoactive intestinal peptide (VIP) acts as an antiproliferative agent in renal cancer cells. This study was designed to evaluate the renoprotective activity of VIP against H2O2-induced oxidative damage in a proximal tubule kidney cell line (human, non-tumor, HK2 cells) in order to investigate the potential usefulness of this peptide in the treatment of oxidative-stress related kidney diseases. HK2 cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Propidium iodide was used to identify cells undergoing apoptosis. Western blotting was performed with anti-Bcl-2, anti-Bax and anti-formyl peptide receptor (low-affinity variant FPRL-1) monoclonal antibodies whereas 2,7-dichlorofluorescein diacetate was used for measurement of levels of intracellular reactive oxygen species (ROS). HK2 cells were injured with H2O2 in order to induce apoptosis: the effect was time- and dose-dependent. VIP increased the levels of the antiapoptotic protein Bcl-2 and decreased those of the proapoptotic protein Bax. VIP decreased the intracellular ROS levels reached by H2O2-induced oxidative stress. VIP effect on ROS levels involved FPLR-1 but not VPAC1,2 receptors as evidenced by the use of the respective antagonists WRW4 and JV-1-53. Thus, VIP protects HK2 cells from apoptosis by increasing Bcl-2 levels and this effect is initiated through FPLR1 receptor. In conclusion, VIP might exert a renoprotective effect by the suppression of oxidative stress. 相似文献