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Axel Baumann Silke Kerruth J?rg Fitter Georg Büldt Joachim Heberle Ramona Schlesinger Kenichi Ataka 《PloS one》2016,11(3)
Proper insertion, folding and assembly of functional proteins in biological membranes are key processes to warrant activity of a living cell. Here, we present a novel approach to trace folding and insertion of a nascent membrane protein leaving the ribosome and penetrating the bilayer. Surface Enhanced IR Absorption Spectroscopy selectively monitored insertion and folding of membrane proteins during cell-free expression in a label-free and non-invasive manner. Protein synthesis was performed in an optical cell containing a prism covered with a thin gold film with nanodiscs on top, providing an artificial lipid bilayer for folding. In a pilot experiment, the folding pathway of bacteriorhodopsin via various secondary and tertiary structures was visualized. Thus, a methodology is established with which the folding reaction of other more complex membrane proteins can be observed during protein biosynthesis (in situ and in operando) at molecular resolution. 相似文献
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Kouji Ohnishi Yasunao Hattori Kazuya Kobayashi Kenichi Akaji 《Bioorganic & medicinal chemistry》2019,27(2):425-435
A non-prime site substituent and warheads combined with a decahydroisoquinolin scaffold was evaluated as a novel inhibitor for severe acute respiratory syndrome (SARS) chymotrypsin-like protease (3CLpro). The decahydroisoquinolin scaffold has been demonstrated to be an effective hydrophobic center to interact with S2 site of SARS 3CLpro, but the lack of interactions at S3 to S4 site is thought to be a major reason for the moderate inhibitory activity. In this study, the effects of an additional non-prime site substituent on the scaffold as well as effects of several warheads are evaluated. For the introduction of a desired non-prime site substituent, amino functionality was introduced on the decahydroisoquinolin scaffold, and the scaffold was constructed by Pd(II) catalyzed diastereoselective ring formation. The synthesized decahydroisoquinolin inhibitors showed about 2.4 times potent inhibitory activities for SARS 3CLpro when combined with a non-prime site substituent. The present results indicated not only the expected additional interactions with the SARS 3CLpro but also the possibility of new inhibitors containing a fused-ring system as a hydrophobic scaffold and a new warhead such as thioacetal. 相似文献
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Murakami Shinsuke Nakatani Jun Nakajima Kenichi Amasawa Eri Ii Ryota Hayashi Kiyotada Yoshikawa Naoki Daigo Ichiro Kishita Yusuke Ihara Tomohiko Shobatake Koichi Kudoh Yuki Motoshita Masaharu Kanemoto Keiichiro Hara Minako Kashiwagi Aiichiro Hashimoto Seiji Shigetomi Yosuke Kanzaki Masayuki Kikuchi Yasunori Ohno Hajime Fukushima Yasuhiro 《The International Journal of Life Cycle Assessment》2019,24(8):1544-1552
The International Journal of Life Cycle Assessment - 相似文献
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Munkhzul Ganbold Yasuhiro Shimamoto Farhana Ferdousi Kenichi Tominaga Hiroko Isoda 《Biochemistry and Biophysics Reports》2019
Quercetin (QCT) and isorhamnetin (ISO), natural flavonoids, were both shown to possess antifibrotic activity in in vivo and in vitro models of hepatic fibrosis. Although ISO is a direct metabolite of QCT differing by a methyl group, it has been reported to be absorbed more adequately and eliminated slower than QCT after oral administration. Our aim of the study was to investigate biological effect of mono-methylated QCT derivatives against fibrosis using rat hepatic stellate cells (HSC-T6). All test derivatives were synthesized from QCT. HSC-T6 cells were induced by TGFβ and treated with derivatives followed by cell proliferation assay, immunofluorescence staining of αSMA, and gene expression analysis of fibrosis markers. All compounds showed a dose- and time-dependent antiproliferation effect. ISO, 3-O-methylquercetin (3MQ), and rhamnetin (RHA) reduced αSMA mRNA; 3MQ prevented the augmentation of collagen I mRNA; and compounds, except azaleatin and 3MQ, reduced Timp1 mRNA expression in TGFβ-induced HSCs. In conclusion, each compound had singular effect against different features of fibrosis depending on the position of methyl group although the further mechanism of action of compounds during fibrosis development remains to be investigated. These findings suggest that antifibrotic effect of quercetin can be enhanced by adding methyl group on functionally important position. 相似文献
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Kenichi Sugawara Shigeo Tanabe Tomotaka Suzuki Toshio Higashi 《Somatosensory & motor research》2019,36(2):109-115
Voluntary motor drive is an important central command that descends via the corticospinal tract to initiate muscle contraction. When electrical stimulation (ES) is applied to an antagonist or agonist muscle, it changes the agonist muscle’s representative motor cortex and thus its voluntary motor drive. In this study, we used a reaction time task to compare the effects of weak and strong ES of the antagonist or agonist muscle during the premotor period of a wrist extension. We recorded motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) that was applied to the extensor carpi radialis (ECR; agonist) and flexor carpi radialis (FCR; antagonist). When stronger ES intensities were applied to the antagonist, the MEP control ratio in the ECR significantly increased during the premotor time. Furthermore, the MEP control ratio with stronger antagonist ES intensity was significantly larger than that in the agonist for the same ES intensity. In the FCR, the MEP control ratio was also significantly greater at the strong ES intensity than at the weak ES intensity. Furthermore, the MEP control ratio in the antagonist with a strong ES intensity was significantly larger than that in the agonist with the same ES intensity. These results suggest that agonist corticomotor excitability might be enhanced by ES of the antagonist, which in turn strongly activates the descending motor system in the preparation of agonist contraction. 相似文献
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