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991.
Boyle KA Stanitsa ES Greseth MD Lindgren JK Traktman P 《The Journal of biological chemistry》2011,286(28):24702-24713
The vaccinia virus DNA polymerase is inherently distributive but acquires processivity by associating with a heterodimeric processivity factor comprised of the viral A20 and D4 proteins. D4 is also an enzymatically active uracil DNA glycosylase (UDG). The presence of an active repair protein as an essential component of the polymerase holoenzyme is a unique feature of the replication machinery. We have shown previously that the A20-UDG complex has a stoichiometry of ~1:1, and our data suggest that A20 serves as a bridge between polymerase and UDG. Here we show that conserved hydrophobic residues in the N' terminus of A20 are important for its binding to UDG. Our data argue against the assembly of D4 into higher order multimers, suggesting that the processivity factor does not form a toroidal ring around the DNA. Instead, we hypothesize that the intrinsic, processive DNA scanning activity of UDG tethers the holoenzyme to the DNA template. The inclusion of UDG as an essential holoenzyme component suggests that replication and base excision repair may be coupled. Here we show that the DNA polymerase can utilize dUTP as a substrate in vitro. Moreover, uracil moieties incorporated into the nascent strand during holoenzyme-mediated DNA synthesis can be excised by the viral UDG present within this holoenzyme, leaving abasic sites. Finally, we show that the polymerase stalls upon encountering an abasic site in the template strand, indicating that, like many replicative polymerases, the poxviral holoenzyme cannot perform translesion synthesis across an abasic site. 相似文献
992.
Ryu SY Beutner G Kinnally KW Dirksen RT Sheu SS 《The Journal of biological chemistry》2011,286(24):21324-21329
Heart mitochondria utilize multiple Ca(2+) transport mechanisms. Among them, the mitochondrial ryanodine receptor provides a fast Ca(2+) uptake pathway across the inner membrane to control "excitation and metabolism coupling." In the present study, we identified a novel ryanodine-sensitive channel in the native inner membrane of heart mitochondria and characterized its pharmacological and biophysical properties by directly patch clamping mitoplasts. Four distinct channel conductances of ~100, ~225, ~700, and ~1,000 picosiemens (pS) in symmetrical 150 mm CsCl were observed. The 225 pS cation-selective channel exhibited multiple subconductance states and was blocked by high concentrations of ryanodine and ruthenium red, known inhibitors of ryanodine receptors. Ryanodine exhibited a concentration-dependent modulation of this channel, with low concentrations stabilizing a subconductance state and high concentrations abolishing activity. The 100, 700, and 1,000 pS conductances exhibited different channel characteristics and were not inhibited by ryanodine. Taken together, these findings identified a novel 225 pS channel as the native mitochondrial ryanodine receptor channel activity in heart mitoplasts with biophysical and pharmacological properties that distinguish it from previously identified mitochondrial ion channels. 相似文献
993.
994.
Neel G Barnaby Fanglian He Xiaowen Liu Kathleen A Wilson Karl A Wilson Anna Tan-Wilson 《Plant Physiology and Biochemistry》2004,42(2):125-134
Protease C1 (E.C. 3.4.21.25), the soybean (Glycine max L. Merrill) proteolytic enzyme responsible for initiating the degradation of soybean storage proteins in seedling cotyledons appears at even higher levels in seedling leaves. This was manifested at the mRNA level through northern blot analysis, at the protein level through western blot analysis, through determination of enzyme activity, and also through isolation and partial sequencing of active leaf enzyme. Comparison of cDNA and amino acid sequences, as well as characterization of enzyme activity, is consistent with the leaf enzyme being identical to or highly similar to the cotyledon enzyme. Protease C1 mRNA and protein are also present in stems of soybean seedlings, but is very low to absent in the roots. This presence in the aerial tissues is consistent with the higher steady state level of gene expression at both the mRNA and protein levels when the seedlings are grown in a 12-h light: 12-h dark photoperiod as compared to seedlings grown in continuous darkness. Transfer of dark-grown seedlings to light is followed by marked elevation in protease C1 protein as seen in western blots. 相似文献
995.
996.
Controlling the intracellular localization of fluorescent polyamide analogues in cultured cells 总被引:4,自引:0,他引:4
Crowley KS Phillion DP Woodard SS Schweitzer BA Singh M Shabany H Burnette B Hippenmeyer P Heitmeier M Bashkin JK 《Bioorganic & medicinal chemistry letters》2003,13(9):1565-1570
The intracellular distribution of fluorescent-labeled polyamides was examined in live cells. We showed that BODIPY-labeled polyamides accumulate in acidic vesicles, mainly lysosomes, in the cytoplasm of HCT116 colon cancer cells and human rheumatoid synovial fibroblasts (RSF). Verapamil blocked vesicular accumulation and led to nuclear accumulation of the BODIPY-labeled polyamide in RSFs. We infer that the basic amine group commonly found at the end of synthetic polyamide chains is responsible for their accumulation in cytoplasmic vesicles in mammalian cells. Modifying the charge on a polyamide by replacing the BODIPY moiety with a fluorescein moiety on the amine tail allowed the polyamide to localize in the nucleus of the cell and bypass the cytoplasmic vesicles in HCT116 cells. 相似文献
997.
Singh U Raju B Lam S Zhou J Gadwood RC Ford CW Zurenko GE Schaadt RD Morin SE Adams WJ Friis JM Courtney M Palandra J Hackbarth CJ Lopez S Wu C Mortell KH Trias J Yuan Z Patel DV Gordeev MF 《Bioorganic & medicinal chemistry letters》2003,13(23):4209-4212
Combinatorial libraries of N-acylated 5-(S)-aminomethyloxazolidinone derivatives of S-oxide and S,S-dioxide tetrahydro-4(2H)-thiopyranyl and thiomorpholine phenyloxazolidinone series have been synthesized on a solid phase and evaluated for antimicrobial activity. Several novel potent leads have been identified, including orally active oxazolidinones with enhanced activity against respiratory tract infection pathogens Haemophilus influenzae and Moraxella catarrhalis. 相似文献
998.
Ralf Rabus Kathleen Trautwein Lars Wöhlbrand 《Applied microbiology and biotechnology》2014,98(8):3371-3388
The denitrifying betaproteobacterium “Aromatoleum aromaticum” EbN1 is a well-studied model organism for anaerobic degradation of aromatic compounds. Following publication of its genome in 2005, comprehensive physiological–proteomic studies were conducted to deduce functional understanding from the genomic blueprint. A catabolic network (85 predicted, 65 identified proteins) for anaerobic degradation of 24 aromatic growth substrates (including 11 newly recognized) was established. Newly elucidated pathways include those for 4-ethylphenol and plant-derived 3-phenylpropanoids, involving functional assignment of several paralogous genes. The substrate-specific regulation of individual peripheral degradation pathways is probably initiated by highly specific chemical sensing via dedicated sensory/regulatory proteins, e.g. three different σ54-dependent one-component sensory/regulatory proteins are predicted to discriminate between three phenolic substrates (phenol, p-cresol and 4-ethylphenol) and two different two-component systems are assumed to differentiate between two alkylbenzenes (toluene, ethylbenzene). Investigations under in situ relevant growth conditions revealed (a) preferred utilization of benzoate from a mixture with succinate results from repressed synthesis of a C4-dicarboxylate TRAP transporter; (b) response to alkylbenzene-induced solvent stress comprises metabolic re-routing of acetyl-CoA and reducing equivalents to poly(3-hydroxybutyrate) synthesis, alteration of cellular membrane composition and formation of putative solvent efflux systems; and (c) multifaceted adaptation to slow growth includes adjustment of energy demand for maintenance and preparedness for future nutritional opportunities, i.e. provision of uptake systems and catabolic enzymes for multiple aromatic substrates despite their absence. This broad knowledge base taken together with the recent development of a genetic system will facilitate future functional, biotechnological (stereospecific dehydrogenases) and habitat re-enacting (“eco-”systems biology) studies with “A. aromaticum” EbN1. 相似文献
999.
Yusuke Kageyama Shaida A Andrabi Weiran Chen Ahmet Höke Valina L Dawson Ted M Dawson Kathleen Gabrielson David A Kass Miho Iijima Hiromi Sesaki 《The EMBO journal》2014,33(23):2798-2813
Mitochondrial dynamics and mitophagy have been linked to cardiovascular and neurodegenerative diseases. Here, we demonstrate that the mitochondrial division dynamin Drp1 and the Parkinson's disease‐associated E3 ubiquitin ligase parkin synergistically maintain the integrity of mitochondrial structure and function in mouse heart and brain. Mice lacking cardiac Drp1 exhibited lethal heart defects. In Drp1KO cardiomyocytes, mitochondria increased their connectivity, accumulated ubiquitinated proteins, and decreased their respiration. In contrast to the current views of the role of parkin in ubiquitination of mitochondrial proteins, mitochondrial ubiquitination was independent of parkin in Drp1KO hearts, and simultaneous loss of Drp1 and parkin worsened cardiac defects. Drp1 and parkin also play synergistic roles in neuronal mitochondrial homeostasis and survival. Mitochondrial degradation was further decreased by combination of Drp1 and parkin deficiency, compared with their single loss. Thus, the physiological importance of parkin in mitochondrial homeostasis is revealed in the absence of mitochondrial division in mammals. 相似文献
1000.
Gregory M. Peters Kathleen R. Murphy Anders Peter S. Adamsen Sander Bruun Magdalena Svanström Marieke ten Hoeve 《The International Journal of Life Cycle Assessment》2014,19(11):1891-1900