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41.
Slicer and the argonautes 总被引:1,自引:0,他引:1
Though they started out as somewhat mysterious components of the RNAi effector complexes, Argonaute proteins have since taken center stage in RNAi gene silencing. They interact with small RNAs to effect gene silencing in all RNAi-related pathways known so far. We will review the dramatic advances in our understanding of the role of the Argonautes in RNAi through studies of their structure and function. 相似文献
42.
Maharjan S Aryal N Bhattarai S Koju D Lamichhane J Sohng JK 《Applied microbiology and biotechnology》2012,93(2):687-696
A number of structurally diverse natural products harboring pyrrole moieties possess a wide range of biological activities.
Studies on biosynthesis of pyrrole ring have shown that pyrrole moieties are derived from l-proline. Nargenicin A1, a saturated alicyclic polyketide from Nocardia sp. CS682, is a pyrrole-2-carboxylate ester of nodusmicin. We cloned and identified a set of four genes from Nocardia sp. CS682 that show sequence similarity to the respective genes involved in the biosynthesis of the pyrrole moieties of pyoluteorin
in Pseudomonas fluorescens, clorobiocin in Streptomyces roseochromogenes subsp. Oscitans, coumermycin A1 in Streptomyces rishiriensis, one of the pyrrole rings of undecylprodigiosin in Streptomyces coelicolor, and leupyrrins in Sorangium cellulosum. These genes were designated as ngnN4, ngnN5, ngnN3, and ngnN2. In this study, we presented the evidences that the pyrrole moiety of nargenicin A1 was also derived from l-proline by the coordinated action of three proteins, NgnN4 (proline adenyltransferase), NgnN5 (proline carrier protein),
and NgnN3 (flavine-dependent acyl-coenzyme A dehydrogenases). Biosynthesis of pyrrole moiety in nargenicin A1 is initiated by NgnN4 that catalyzes ATP-dependent activation of l-proline into l-prolyl-AMP, and the latter is transferred to NgnN5 to create prolyl-S-peptidyl carrier protein (PCP). Later, NgnN3 catalyzes the two-step oxidation of prolyl-S-PCP into pyrrole-2-carboxylate. Thus, this study presents another example of a pyrrole moiety biosynthetic pathway that uses
a set of three genes to convert l-proline into pyrrole-2-carboxylic acid moiety. 相似文献
43.
Larisa Adamian Hélène A. Gussin Yan Yuan Tseng Niraj J. Muni Feng Feng Haohua Qian David R. Pepperberg Jie Liang 《Protein science : a publication of the Protein Society》2009,18(11):2371-2383
The homopentameric ρ1 GABAC receptor is a ligand‐gated ion channel with a binding pocket for γ‐aminobutyric acid (GABA) at the interfaces of N‐terminal extracellular domains. We combined evolutionary analysis, structural modeling, and experimental testing to study determinants of GABAC receptor assembly and channel gating. We estimated the posterior probability of selection pressure at amino acid residue sites measured as ω‐values and built a comparative structural model, which identified several polar residues under strong selection pressure at the subunit interfaces that may form intersubunit hydrogen bonds or salt bridges. At three selected sites (R111, T151, and E55), mutations disrupting intersubunit interactions had strong effects on receptor folding, assembly, and function. We next examined the role of a predicted intersubunit salt bridge for residue pair R158–D204. The mutant R158D, where the positively charged residue is replaced by a negatively charged aspartate, yielded a partially degraded receptor and lacked membrane surface expression. The membrane surface expression was rescued by the double mutant R158D–D204R, where positive and negative charges are switched, although the mutant receptor was inactive. The single mutants R158A, D204R, and D204A exhibited diminished activities and altered kinetic profiles with fast recovery kinetics, suggesting that R158–D204 salt bridge perhaps stabilizes the open state of the GABAC receptor. Our results emphasize the functional importance of highly conserved polar residues at the protein–protein interfaces in GABAC ρ1 receptors and demonstrate how the integration of computational and experimental approaches can aid discovery of functionally important interactions. 相似文献
44.
Parajuli D Adhikari CR Kawakita H Yamada S Ohto K Inoue K 《Bioresource technology》2009,100(2):1000-1002
Recovery of Au(III) from hydrochloric acid medium by using crosslinked chestnut pellicle (CCP) gel was studied. Strong selectivity was observed for Au(III) showing negligible affinity for other precious metals and some base metal ions tested. The adsorption isotherm study exhibited the maximum loading capacity of the gel as high as 10.6 mol or about 2.1 kg gold per kg dry weight of gel. The reduction of Au(III) ion to elemental form during adsorption process is expected to be the reason of high selectivity and high capacity for Au(III). Kinetic studies at various temperatures confirm an endothermic adsorption process following the pseudo-first order rate law. 相似文献
45.
Chandan Singh Ved Prakash Verma Niraj Krishna Naikade Ajit Shankar Singh Mohammad Hassam Sunil. K. Puri 《Bioorganic & medicinal chemistry letters》2010,20(15):4459-4463
A new series of 6-(4′-aryloxy-phenyl)vinyl-1,2,4-trioxanes 10a–d, 11a–d, and 12a–d have been synthesized and evaluated for their antimalarial activity against multidrug-resistant Plasmodium yoelii in Swiss mice by oral route. Trioxanes 10b and 10c, the two most active compounds of the series, provided 100% protection to the infected mice at 48 mg/kg × 4 days. Clinically useful drug β-arteether provided 100% and 20% protection at 48 mg/kg × 4 days and 24 mg/kg × 4 days, respectively, in this model. 相似文献
46.
The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding motif in RNAi effector complexes 总被引:28,自引:0,他引:28
Song JJ Liu J Tolia NH Schneiderman J Smith SK Martienssen RA Hannon GJ Joshua-Tor L 《Nature structural biology》2003,10(12):1026-1032
RISC, the RNA-induced silencing complex, uses short interfering RNAs (siRNAs) or micro RNAs (miRNAs) to select its targets in a sequence-dependent manner. Key RISC components are Argonaute proteins, which contain two characteristic domains, PAZ and PIWI. PAZ is highly conserved and is found only in Argonaute proteins and Dicer. We have solved the crystal structure of the PAZ domain of Drosophila Argonaute2. The PAZ domain contains a variant of the OB fold, a module that often binds single-stranded nucleic acids. PAZ domains show low-affinity nucleic acid binding, probably interacting with the 3' ends of single-stranded regions of RNA. PAZ can bind the characteristic two-base 3' overhangs of siRNAs, indicating that although PAZ may not be a primary nucleic acid binding site in Dicer or RISC, it may contribute to the specific and productive incorporation of siRNAs and miRNAs into the RNAi pathway. 相似文献
47.
48.
Bidur Parajuli Hyun-Gyo Lee Sang-Hoon Kwon Soon-Do Cha So-Jin Shin Gun-Ho Lee Insoo Bae Chi-Heum Cho 《Cancer epidemiology》2013,37(4):512-517
BackgroundDespite advances in treatment, ovarian cancer is the most lethal gynecologic malignancy. Therefore significant efforts are being made to develop novel strategies for the treatment of ovarian cancer. Salinomycin has been shown to be highly effective in the elimination of cancer stem cells both in vitro and in vivo. The present study focused on investigating important cell signaling molecules such as Akt and NF-κB during salinomycin-induced apoptosis in cisplatin resistant ovarian cancer cells (A2780cis).MethodsMTT assay was performed to determine cell viability. Flow cytometry and DNA fragmentation assay were performed to analyze the effect on cell cycle and apoptosis. The expression of apoptosis related proteins was evaluated by Western blot analysis.ResultsThe cell viability was significantly reduced by salinomycin treatment in a dose dependent manner. The flow cytometry result showed an increase in sub-G1 phase. Salinomycin inhibited the nuclear transportation of NF-κB, and downregulated Akt expression. Declined Bcl-2, activation of caspase-3 and increased PARP cleavage triggered apoptosis. Moreover, DNA fragmentation assay also revealed apoptotic induction.ConclusionThe result suggested that salinomycin-induced apoptosis in A2780cis was associated with inhibition of Akt/NF-κB. It may become a potential chemotherapeutic agent for the cisplatin resistant ovarian cancer therapy. 相似文献
49.
Hiroshi Horiuchi Bijay Parajuli Yue Wang Yasu-Taka Azuma Tetsuya Mizuno Hideyuki Takeuchi Akio Suzumura 《PloS one》2015,10(3)
Activated microglia can exert either neurotoxic or neuroprotective effects, and they play pivotal roles in the pathogenesis and progression of various neurological diseases. In this study, we used cDNA microarrays to show that interleukin-19 (IL-19), an IL-10 family cytokine, is markedly upregulated in activated microglia. Furthermore, we found that microglia are the only cells in the nervous system that express the IL-19 receptor, a heterodimer of the IL-20Rα and IL-20Rβ subunits. IL-19 deficiency increased the production of such pro-inflammatory cytokines as IL-6 and tumor necrosis factor-α in activated microglia, and IL-19 treatment suppressed this effect. Moreover, in a mouse model of Alzheimer’s disease, we observed upregulation of IL-19 in affected areas in association with disease progression. Our findings demonstrate that IL-19 is an anti-inflammatory cytokine, produced by activated microglia, that acts negatively on microglia in an autocrine manner. Thus, microglia may self-limit their inflammatory response by producing the negative regulator IL-19. 相似文献
50.
Michael Seimetz Nirmal Parajuli Alexandra Pichl Mariola Bednorz Hossein Ardeschir Ghofrani Ralph Theo Schermuly Werner Seeger Friedrich Grimminger Norbert Weissmann 《PloS one》2015,10(6)