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891.
Background
The human pathogen Mycobacterium tuberculosis (Mtb) has the originality of possessing a multifunctional mega-enzyme FAS-I (Fatty Acid Synthase-I), together with a multi-protein FAS-II system, to carry out the biosynthesis of common and of specific long chain fatty acids: the mycolic acids (MA). MA are the main constituents of the external mycomembrane that represents a tight permeability barrier involved in the pathogenicity of Mtb. The MA biosynthesis pathway is essential and contains targets for efficient antibiotics. We have demonstrated previously that proteins of FAS-II interact specifically to form specialized and interconnected complexes. This finding suggested that the organization of FAS-II resemble to the architecture of multifunctional mega-enzyme like the mammalian mFAS-I, which is devoted to the fatty acid biosynthesis.Principal Findings
Based on conventional and reliable studies using yeast-two hybrid, yeast-three-hybrid and in vitro Co-immunoprecipitation, we completed here the analysis of the composition and architecture of the interactome between the known components of the Mtb FAS-II complexes. We showed that the recently identified dehydratases HadAB and HadBC are part of the FAS-II elongation complexes and may represent a specific link between the core of FAS-II and the condensing enzymes of the system. By testing four additional methyltransferases involved in the biosynthesis of mycolic acids, we demonstrated that they display specific interactions with each type of complexes suggesting their coordinated action during MA elongation.Significance
These results provide a global update of the architecture and organization of a FAS-II system. The FAS-II system of Mtb is organized in specialized interconnected complexes and the specificity of each elongation complex is given by preferential interactions between condensing enzymes and dehydratase heterodimers. This study will probably allow defining essential and specific interactions that correspond to promising targets for Mtb FAS-II inhibitors. 相似文献892.
Algicidal Activity of Thiazolidinedione Derivatives Against Harmful Algal Blooming Species 总被引:1,自引:0,他引:1
Kim YM Wu Y Duong TU Jung SG Kim SW Cho H Jin E 《Marine biotechnology (New York, N.Y.)》2012,14(3):312-322
Thiazolidinedione (TD) derivatives exhibit algicidal activity against harmful algal blooming species such as Chattonella marina, Heterosigma akashiwo, and Cochlodinium polykrikoides, as reported previously. In this study, the efficacies and selectivities of TD derivatives were tested by analyzing the structure–activity relationships of various TD derivatives. To investigate structure–activity relationships for growth inhibition of harmful algae, we added a methylene group between the cyclohexyl ring and oxygen of 5-(3-chloro-4-hydroxybenzylidene)-TD, which decreased the inhibitory potency of compound 17. Interestingly, another addition of a methylene group significantly increased the inhibitory potency against C. polykrikoides. The addition of 1 μM compound 17 resulted in the cell rupture of harmful algae after less than 10 h incubation at 20 °C. Compound 17 was applied to both harmful and non-harmful algae and showed a drastic reduction in the efficiency of photosystem II, resulting in reduced photosynthetic oxygen evolution. Compound 17 at a 5 μM concentration destroyed all of the harmful algae, while algicidal activity against non-harmful algae did not exceed 30% of the control within the concentration range tested. In contrast, a herbicide, 3-(3,4-dichlorophenyl)-1,1-dimethylurea, tested at a 5 μM concentration, exhibited 40–70% algicidal activity relative to that of the control against both harmful and non-harmful algae. Compound 17 is a promising lead compound for the development of algicides to control harmful algal blooming species. 相似文献
893.
Thyroid hormone (T3) has a major influence on cerebellum post-natal development. The major phenotypic landmark of exposure to low levels of T3 during development (hypothyroidism) in the cerebellum is the retarded inward migration of the most numerous cell type, granular neurons. In order to identify the direct genetic regulation exerted by T3 on cerebellar neurons and their precursors, we used microarray RNA hybridization to perform a time course analysis of T3 induced gene expression in primary cultures of cerebellar neuronal cell. These experiments suggest that we identified a small set of genes which are directly regulated, both in vivo and in vitro, during cerebellum post-natal development. These modest changes suggest that T3 does not acts directly on granular neurons and mainly indirectly influences the cellular interactions taking place during development. 相似文献
894.
Pierre-Fran?ois Lesault Marine Theret Mélanie Magnan Sylvain Cuvellier Yiming Niu Romain K. Gherardi Jacques P. Tremblay Luc Hittinger Bénédicte Chazaud 《PloS one》2012,7(10)
Transplantation of muscle precursor cells is of therapeutic interest for focal skeletal muscular diseases. However, major limitations of cell transplantation are the poor survival, expansion and migration of the injected cells. The massive and early death of transplanted myoblasts is not fully understood although several mechanisms have been suggested. Various attempts have been made to improve their survival or migration. Taking into account that muscle regeneration is associated with the presence of macrophages, which are helpful in repairing the muscle by both cleansing the debris and deliver trophic cues to myoblasts in a sequential way, we attempted in the present work to improve myoblast transplantation by coinjecting macrophages. The present data showed that in the 5 days following the transplantation, macrophages efficiently improved: i) myoblast survival by limiting their massive death, ii) myoblast expansion within the tissue and iii) myoblast migration in the dystrophic muscle. This was confirmed by in vitro analyses showing that macrophages stimulated myoblast adhesion and migration. As a result, myoblast contribution to regenerating host myofibres was increased by macrophages one month after transplantation. Altogether, these data demonstrate that macrophages are beneficial during the early steps of myoblast transplantation into skeletal muscle, showing that coinjecting these stromal cells may be used as a helper to improve the efficiency of parenchymal cell engraftment. 相似文献
895.
Duong A Capstick DS Di Berardo C Findlay KC Hesketh A Hong HJ Elliot MA 《Molecular microbiology》2012,83(5):992-1005
Streptomyces coelicolor is a multicellular bacterium whose life cycle encompasses three differentiated states: vegetative hyphae, aerial hyphae and spores. Among the factors required for aerial development are the 'chaplins', a family of eight secreted proteins that coat the surface of aerial hyphae. Three chaplins (the 'long' chaplins, ChpA, B and C) possess an LAXTG-containing C-terminal sorting signal and are predicted sortase substrates. The five remaining 'short' chaplins are presumed to be associated with the cell surface through interactions with the long chaplins. We show here that two sortase enzymes, SrtE1 and SrtE2, cleave LAXTG-containing peptides at two distinct positions in vitro, and are required for cell wall anchoring of ChpC in vivo. srtE1/E2 double mutants are delayed in aerial hyphae formation, do not sporulate and fail to display all short chaplins on their aerial surfaces. Surprisingly, these mutant characteristics were not shared by a long chaplin mutant, which exhibited only modest delays in aerial development, leading us to revise the current model of chaplin-mediated aerial development. The sortase mutant phenotype, instead, appears to stem from an inability to transcribe aerial hyphae-specific genes, whose products have diverse functions. This suggests that sortase activity triggers an important, and previously unknown, developmental checkpoint. 相似文献
896.
Vialart G Hehn A Olry A Ito K Krieger C Larbat R Paris C Shimizu B Sugimoto Y Mizutani M Bourgaud F 《The Plant journal : for cell and molecular biology》2012,70(3):460-470
Coumarins are important compounds that contribute to the adaptation of plants to biotic or abiotic stresses. Among coumarins, umbelliferone occupies a pivotal position in the plant phenylpropanoid network. Previous studies indicated that umbelliferone is derived from the ortho‐hydroxylation of p‐coumaric acid by an unknown biochemical step to yield 2,4‐dihydroxycinnamic acid, which then undergoes spontaneous lactonization. Based on a recent report of a gene encoding a 2‐oxoglutarate‐dependent dioxygenase from Arabidopsis thaliana that exhibited feruloyl CoA 6′‐hydroxylase activity ( Bourgaud et al., 2006 ), we combined a bioinformatic approach and a cDNA library screen to identify an orthologous ORF (Genbank accession number JF799117 ) from Ruta graveolens L. This ORF shares 59% amino acid identity with feruloyl CoA 6′‐hydroxylase, was functionally expressed in Escherichia coli, and converted feruloyl CoA into scopoletin and p‐coumaroyl CoA into umbelliferone with equal activity. Its bi‐functionality was further confirmed in planta: transient expression of JF799117 in Nicotiana benthamiana yielded plants with leaves containing high levels of umbelliferone and scopoletin when compared to control plants, which contained barely detectable traces of these compounds. The expression of JF799117 was also tightly correlated to the amount of umbelliferone that was found in UV‐elicited R. graveolens leaves. Therefore, JF799117 encodes a p‐coumaroyl CoA 2′‐hydroxylase in R. graveolens, which represents a previously uncharacterized step in the synthesis of umbelliferone in plants. Psoralen, which is an important furanocoumarin in R. graveolens, was found to be a competitive inhibitor of the enzyme, and it may exert this effect through negative feedback on the enzyme at an upstream position in the pathway. 相似文献
897.
Noel R Song X Shin Y Banerjee S Kojetin D Lin L Ruiz CH Cameron MD Burris TP Kamenecka TM 《Bioorganic & medicinal chemistry letters》2012,22(11):3739-3742
The design and synthesis of a novel series of Rev-erbα agonists is described. The development and optimization of the tetrahydroisoquinoline series was carried out from an earlier acyclic series of Rev-erbα agonists. Through the optimization of the scaffold 1, several potent compounds with good in vivo profiles were discovered. 相似文献
898.
Boichard D Chung H Dassonneville R David X Eggen A Fritz S Gietzen KJ Hayes BJ Lawley CT Sonstegard TS Van Tassell CP VanRaden PM Viaud-Martinez KA Wiggans GR;Bovine LD Consortium 《PloS one》2012,7(3):e34130
The Illumina BovineLD BeadChip was designed to support imputation to higher density genotypes in dairy and beef breeds by including single-nucleotide polymorphisms (SNPs) that had a high minor allele frequency as well as uniform spacing across the genome except at the ends of the chromosome where densities were increased. The chip also includes SNPs on the Y chromosome and mitochondrial DNA loci that are useful for determining subspecies classification and certain paternal and maternal breed lineages. The total number of SNPs was 6,909. Accuracy of imputation to Illumina BovineSNP50 genotypes using the BovineLD chip was over 97% for most dairy and beef populations. The BovineLD imputations were about 3 percentage points more accurate than those from the Illumina GoldenGate Bovine3K BeadChip across multiple populations. The improvement was greatest when neither parent was genotyped. The minor allele frequencies were similar across taurine beef and dairy breeds as was the proportion of SNPs that were polymorphic. The new BovineLD chip should facilitate low-cost genomic selection in taurine beef and dairy cattle. 相似文献
899.
900.