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31.
Prudent R Moucadel V López-Ramos M Aci S Laudet B Mouawad L Barette C Einhorn J Einhorn C Denis JN Bisson G Schmidt F Roy S Lafanechere L Florent JC Cochet C 《Molecular and cellular biochemistry》2008,316(1-2):71-85
None of the already described CK2 inhibitors did fulfill the requirements for successful clinical settings. In order to find innovative CK2 inhibitors based on new scaffolds, we have performed a high-throughput screening of diverse chemical libraries. We report here the identification and characterization of several classes of new inhibitors. Whereas some share characteristics of previously known CK2 inhibitors, others are chemically unrelated and may represent new opportunities for the development of better CK2 inhibitors. By combining structure-activity relationships with a docking procedure, we were able to determine the binding mode of these inhibitors. Interestingly, beside the identification of several nanomolar ATP-competitive inhibitors, one class of chemical inhibitors displays a non-ATP competitive mode of inhibition, a feature that suggests that CK2 possess distinct druggable binding sites. For the most promising inhibitors, selectivity profiling was performed. We also provide evidence that some chemical compounds are inhibiting CK2 in living cells. Finally, the collected data allowed us to draw the rules about the chemical requirements for CK2 inhibition both in vitro and in a cellular context. 相似文献
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Silva Liliane Andrade Lopes Neto Jose Honorio Pereira Cardarelli Haíssa Roberta 《Annals of microbiology》2019,69(4):321-328
Some lactic acid bacteria are capable of producing capsular or extracellular polysaccharides, with desirable technological properties and biological activities. Such polysaccharides produced by lactic acid bacteria are called exopolysaccharides and can be used to alter rheological properties, acting in processes involving viscosity, emulsification, and flocculation, among others. They may also be involved in prebiotic, probiotic, and biological activities, as well as having potential application in the food industry. In this mini-review, the objectives were to present some beneficial properties of exopolysaccharides (EPS) produced by Lactobacillus plantarum that have not been commercially explored. For that, the article focused to summarize revision of current publications within the following topics: (1) rheological properties, (2) prebiotic properties, (3) biological activities, and (4) potential application in the food industry. EPS produced by Lb. plantarum can be used as gelling agent, emulsifier, or stabilizer for food products. The glucan nature of the produced EPS enhances probiotic properties of this LAB species. Lactobacillus plantarum EPS has antioxidant, antibiofilm, and antitumor activities. Finally, there is an improvement in texture of fermented food products where Lb. plantarum is used as starter culture which is related to EPS production in situ. Therefore, EPS produced by Lb. plantarum have important and desirable properties to be explored for several applications, including health and food areas. 相似文献
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SATB1 Cleavage by Caspase 6 Disrupts PDZ Domain-Mediated Dimerization, Causing Detachment from Chromatin Early in T-Cell Apoptosis 下载免费PDF全文
Sanjeev Galande Liliane A. Dickinson I. Saira Mian Marianna Sikorska Terumi Kohwi-Shigematsu 《Molecular and cellular biology》2001,21(16):5591-5604
SATB1 is expressed primarily in thymocytes and orchestrates temporal and spatial expression of a large number of genes in the T-cell lineage. SATB1 binds to the bases of chromatin loop domains in vivo, recognizing a special DNA context with strong base-unpairing propensity. The majority of thymocytes are eliminated by apoptosis due to selection processes in the thymus. We investigated the fate of SATB1 during thymocyte and T-cell apoptosis. Here we show that SATB1 is specifically cleaved by a caspase 6-like protease at amino acid position 254 to produce a 65-kDa major fragment containing both a base-unpairing region (BUR)-binding domain and a homeodomain. We found that this cleavage separates the DNA-binding domains from amino acids 90 to 204, a region which we show to be a dimerization domain. The resulting SATB1 monomer loses its BUR-binding activity, despite containing both its DNA-binding domains, and rapidly dissociates from chromatin in vivo. We found this dimerization region to have sequence similarity to PDZ domains, which have been previously shown to be involved in signaling by conferring protein-protein interactions. SATB1 cleavage during Jurkat T-cell apoptosis induced by an anti-Fas antibody occurs concomitantly with the high-molecular-weight fragmentation of chromatin of ~50-kb fragments. Our results suggest that mechanisms of nuclear degradation early in apoptotic T cells involve efficient removal of SATB1 by disrupting its dimerization and cleavage of genomic DNA into loop domains to ensure rapid and efficient disassembly of higher-order chromatin structure. 相似文献
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Vandingenen A Hens K Baggerman G Macours N Schoofs L De Loof A Huybrechts R 《Peptides》2002,23(10):1853-1863
Vitellogenic ovaries of the gray fleshfly Neobellieria bullata contain a variety of unidentified substances that interact, either as a substrate or as an inhibitor, with angiotensin converting enzyme (ACE). We here report the isolation and characterization of the first ACE interactive compound hereof. This 1312.7 Da peptide with the sequence NKLKPSQWISL, is substrate to both insect and human ACE. It is a novel peptide that shows high sequence similarity to a sequence at the N-terminal part of dipteran yolk polypeptides (YPs). We propose to call it N. bullata ovary-derived ACE interactive factor or Neb-ODAIF. Both insect and human ACE hydrolyze Neb-ODAIF by sequentially cleaving off two C-terminal dipeptides. K(m) values of Neb-ODAIF and Neb-ODAIF(1-9) (NKLKPSQWI) for human somatic ACE (sACE) are 17 and 81 microM, respectively. Additionally, Neb-ODAIF(1-7) (NKLKPSQ) also interacts with sACE (K(m/i)=90 microM). These affinity-constants are in range with those of the physiological ACE substrates and suggest the importance of Neb-ODAIF and its cleavage products in the elucidation of the physiological role of insect ACE. Alternatively, they can serve as lead compounds in the development of new drugs against ACE-related diseases in humans. 相似文献
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We have characterized the maturation, co- and posttranslational modifications, and functional properties of the alpha(1B)-adrenergic receptor (AR) expressed in different mammalian cells transfected using conventional approaches or the Semliki Forest virus system. We found that the alpha(1B)-AR undergoes N-linked glycosylation as demonstrated by its sensitivity to endoglycosidases and by the effect of tunicamycin on receptor maturation. Pulse-chase labeling experiments in BHK-21 cells demonstrate that the alpha(1B)-AR is synthesized as a 70 kDa core glycosylated precursor that is converted to the 90 kDa mature form of the receptor with a half-time of approximately 2 h. N-Linked glycosylation of the alpha(1B)-AR occurs at four asparagines on the N-terminus of the receptor. Mutations of the N-linked glycosylation sites did not have a significant effect on receptor function or expression. Surprisingly, receptor mutants lacking N-linked glycosylation migrated as heterogeneous bands in SDS-PAGE. Our findings demonstrate that N-linked glycosylation and phosphorylation, but not palmitoylation or O-linked glycosylation, contribute to the structural heterogeneity of the alpha(1B)-AR as it is observed in SDS-PAGE. The modifications found are similar in the different mammalian expression systems explored. Our findings indicate that the Semliki Forest virus system can provide large amounts of functional and fully glycosylated alpha(1B)-AR protein suitable for biochemical and structural studies. The results of this study contribute to elucidate the basic steps involved in the processing of G protein-coupled receptors as well as to optimize strategies for their overexpression. 相似文献
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da Silva Gessiane Pereira de Melo Josi Teixeira Monteiro Frederico Ozanan Barros Ferreira Ana Karolyna Pereira Carneiro Liliane Almeida Takeshita Rafaela S. C. 《International journal of primatology》2021,42(5):722-736
International Journal of Primatology - The hormone dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are the most abundant circulating steroids in human and some nonhuman primates, and... 相似文献
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