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151.
Renato F. Freitas Igor M. Prokopczyk Aderson Zottis Glaucius Oliva Adriano D. Andricopulo Maria Teresa S. Trevisan Wagner Vilegas Maria Goretti V. Silva Carlos A. Montanari 《Bioorganic & medicinal chemistry》2009,17(6):2476-2482
Based on its essential role in the life cycle of Trypanosoma cruzi, the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) has been considered a promising target for the development of novel chemotherapeutic agents for the treatment of Chagas’ disease. In the course of our research program to discover novel inhibitors of this trypanosomatid enzyme, we have explored a combination of structure and ligand-based virtual screening techniques as a complementary approach to a biochemical screening of natural products using a standard biochemical assay. Seven natural products, including anacardic acids, flavonoid derivatives, and one glucosylxanthone were identified as novel inhibitors of T. cruzi GAPDH. Promiscuous inhibition induced by nonspecific aggregation has been discarded as specific inhibition was not reversed or affected in all cases in the presence of Triton X-100, demonstrating the ability of the assay to find authentic inhibitors of the enzyme. The structural diversity of this series of promising natural products is of special interest in drug design, and should therefore be useful in future medicinal chemistry efforts aimed at the development of new GAPDH inhibitors having increased potency. 相似文献
152.
Francesco Oliva Loredana Zocchi Eleonora Candi Gerry Melino Umberto Tarantino 《Biochemical and biophysical research communications》2009,379(4):887-891
The ethiopathogenesis of rotator cuff disease remains poorly understood. Many studies advocate the importance of extra cellular matrix for the homeostasis of connective tissue. Transglutaminase enzymes family has been studied in the context of connective tissue formation and stabilisation. Here, we investigated transglutaminases expression pattern in biopsies of normal and injured supraspinatus tendons of human shoulders and in the Achilles tendons of transglutaminase 2 knock-out and wild-type mice. Our results show that different transglutaminase family members are differentially expressed in human and mouse tendons, and that transglutaminase 2 is down-regulated at mRNA and protein levels upon human supraspinatus tendon ruptures. 相似文献
153.
Ney Ribeiro Leite Renata Krogh Wei Xu Yuko Ishida Jorge Iulek Walter S. Leal Glaucius Oliva 《PloS one》2009,4(11)
Background
The yellow fever mosquito, Aedes aegypti, is the primary vector for the viruses that cause yellow fever, mostly in tropical regions of Africa and in parts of South America, and human dengue, which infects 100 million people yearly in the tropics and subtropics. A better understanding of the structural biology of olfactory proteins may pave the way for the development of environmentally-friendly mosquito attractants and repellents, which may ultimately contribute to reduction of mosquito biting and disease transmission.Methodology
Previously, we isolated and cloned a major, female-enriched odorant-binding protein (OBP) from the yellow fever mosquito, AaegOBP1, which was later inadvertently renamed AaegOBP39. We prepared recombinant samples of AaegOBP1 by using an expression system that allows proper formation of disulfide bridges and generates functional OBPs, which are indistinguishable from native OBPs. We crystallized AaegOBP1 and determined its three-dimensional structure at 1.85 Å resolution by molecular replacement based on the structure of the malaria mosquito OBP, AgamOBP1, the only mosquito OBP structure known to date.Conclusion
The structure of AaegOBP1 ( = AaegOBP39) shares the common fold of insect OBPs with six α-helices knitted by three disulfide bonds. A long molecule of polyethylene glycol (PEG) was built into the electron-density maps identified in a long tunnel formed by a crystallographic dimer of AaegOBP1. Circular dichroism analysis indicated that delipidated AaegOBP1 undergoes a pH-dependent conformational change, which may lead to release of odorant at low pH (as in the environment in the vicinity of odorant receptors). A C-terminal loop covers the binding cavity and this “lid” may be opened by disruption of an array of acid-labile hydrogen bonds thus explaining reduced or no binding affinity at low pH. 相似文献154.
155.
Ricardo Oliva Joe Win Sylvain Raffaele Laurence Boutemy Tolga O. Bozkurt Angela Chaparro‐Garcia Maria Eugenia Segretin Remco Stam Sebastian Schornack Liliana M. Cano Mireille van Damme Edgar Huitema Marco Thines Mark J. Banfield Sophien Kamoun 《Cellular microbiology》2010,12(6):705-715
Filamentous pathogens, such as plant pathogenic fungi and oomycetes, secrete an arsenal of effector molecules that modulate host innate immunity and enable parasitic infection. It is now well accepted that these effectors are key pathogenicity determinants that enable parasitic infection. In this review, we report on the most interesting features of a representative set of filamentous pathogen effectors and highlight recent findings. We also list and describe all the linear motifs reported to date in filamentous pathogen effector proteins. Some of these motifs appear to define domains that mediate translocation inside host cells. 相似文献
156.
E. Tomás-Pejó M. Ballesteros J. M. Oliva L. Olsson 《Journal of industrial microbiology & biotechnology》2010,37(11):1211-1220
An efficient fermenting microorganism for bioethanol production from lignocellulose is highly tolerant to the inhibitors released
during pretreatment and is able to ferment efficiently both glucose and xylose. In this study, directed evolution was employed
to improve the xylose fermenting Saccharomyces cerevisiae F12 strain for bioethanol production at high substrate loading. Adapted and parental strains were compared with respect to
xylose consumption and ethanol production. Adaptation led to an evolved strain more tolerant to the toxic compounds present
in the medium. When using concentrated prehydrolysate from steam-pretreated wheat straw with high inhibitor concentration,
an improvement of 65 and 20% in xylose consumption and final ethanol concentration, respectively, were achieved using the
adapted strain. To address the need of high substrate loadings, fed-batch SSF experiments were performed and an ethanol concentration
as high as 27.4 g/l (61% of the theoretical) was obtained with 11.25% (w/w) of water insoluble solids (WIS). 相似文献
157.
158.
Marta Rodríguez-García Núria Climent Harold Oliva Víctor Casanova Rafael Franco Agathe Leon José M. Gatell Felipe García Teresa Gallart 《PloS one》2010,5(2)
Background
Defensins are natural endogenous antimicrobial peptides with potent anti-HIV activity and immuno-modulatory effects. We recently demonstrated that immature dendritic cells (DC) produce α-defensins1-3 and that α-defensins1-3 modulate DC generation and maturation. Since DC-HIV interaction plays a critical role during the first steps of HIV infection, we investigated the possible impact of α-defensins1-3 production by DC on disease progression.Methodology/Principal Findings
Monocyte-derived DC (MDDC) were analyzed comparatively in healthy controls (HC) and HIV-infected patients, including untreated “elite” and “viremic” controllers, untreated viremic non-controllers and antiretroviral-treated patients. We found that production of α-defensins1-3 was significantly increased in MDDC from HIV-infected patients versus HC, and this increase was mainly due to that observed in controllers, while in non-controllers the increase was not statistically significant (controllers vs. HC, p<0.005; controllers vs. non-controllers p<0.05). Secreted α-defensins1-3 by immature MDDC positively correlated with CD4 T cell counts in controllers, but not in non-controllers. Moreover, independently of their clinical classification, HIV-infected patients with higher α-defensins1-3 secretion by immature MDDC showed slower disease progression, measured as no decrease in the number of CD4+ T-cells below 350 cell/mm3, lower increase of plasma viral load and no initiation of treatment over time. Plasma alpha-defensins1-3 levels lacked any relationship with immunologic and virologic parameters.Conclusions/Significance
High production of α-defensins1-3 by immature DCs appears as a host protective factor against progression of HIV-1infection, suggesting potential diagnostic, therapeutic and preventive implications. This protective effect may arise from the activity of α-defensins1-3 to damage the virions prior and/or after their internalization by immature DC, and hence favoring a more efficient viral processing and presentation to HIV-specific CD4+ T cells, without or with a minor rate of transmission of infectious HIV-1 virions. 相似文献159.