• Title/Summary/Keyword: Binding Ability

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Interaction of Hepatitis C Virus Core Protein with Janus Kinase Is Required for Efficient Production of Infectious Viruses

  • Lee, Choongho
    • Biomolecules & Therapeutics
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    • v.21 no.2
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    • pp.97-106
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    • 2013
  • Chronic hepatitis C virus (HCV) infection is responsible for the development of liver cirrhosis and hepatocellular carcinoma. HCV core protein plays not only a structural role in the virion morphogenesis by encapsidating a virus RNA genome but also a non-structural role in HCV-induced pathogenesis by blocking innate immunity. Especially, it has been shown to regulate JAK-STAT signaling pathway through its direct interaction with Janus kinase (JAK) via its proline-rich JAK-binding motif ($^{79}{\underline{P}}GY{\underline{P}}WP^{84}$). However, little is known about the physiological significance of this HCV core-JAK association in the context of the virus life cycle. In order to gain an insight, a mutant HCV genome (J6/JFH1-79A82A) was constructed to express the mutant core with a defective JAK-binding motif ($^{79}{\underline{A}}GY{\underline{A}}WP^{84}$) using an HCV genotype 2a infectious clone (J6/JFH1). When this mutant HCV genome was introduced into hepatocarcinoma cells, it was found to be severely impaired in its ability to produce infectious viruses in spite of its robust RNA genome replication. Taken together, all these results suggest an essential requirement of HCV core-JAK protein interaction for efficient production of infectious viruses and the potential of using core-JAK blockers as a new anti-HCV therapy.

Potentially Multidentate Tripodal Amine Catechol Ligands as Chelators for Ga(III) and In(III)

  • Sahoo, Suban K.;Baral, Minati;Bera, Rati Kanta;Kanungo, B. K.
    • Bulletin of the Korean Chemical Society
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    • v.30 no.9
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    • pp.1956-1962
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    • 2009
  • The binding abilities of two multidentate tripodal amine catechol ligands, cis,cis-1,3,5-tris[(2,3-dihydroxybenzylamino) aminomethyl]cyclohexane (TMACHCAT, $L^1)\;and\;N^1,N^3,N^5$-tris(2-(2,3-dihydroxybenzylamino) ethyl)cyclohexane-1,3,5-tricarboxamide (CYCOENCAT, $L^2$) with Ga(III) and In(III) have been investigated by potentiometric and spectrophotometric methods in an aqueous medium of 0.1 M KCl at 25 ${\pm}\;1\;{^{\circ}C}.$ The ligands $L^1\;and\;L^2$ formed various monomeric species $MLH_3,\;MLH_2$, MLH and ML (M = $Ga^{+3}\;and\;In^{+3}$) and showed potential to form strong encapsulated tris(catechol) type complexes. The coordination modes, binding ability and selectivity of the ligands towards Ga(III) and In(III) have been discussed with the help of experimental evidences, and supported with molecular modeling calculations.

Wogonin Attenuates Hippocampal Neuronal Loss and Cognitive Dysfunction in Trimethyltin-Intoxicated Rats

  • Lee, Bombi;Sur, Bongjun;Cho, Seong-Guk;Yeom, Mijung;Shim, Insop;Lee, Hyejung;Hahm, Dae-Hyun
    • Biomolecules & Therapeutics
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    • v.24 no.3
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    • pp.328-337
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    • 2016
  • We examined whether wogonin (WO) improved hippocampal neuronal activity, behavioral alterations and cognitive impairment, in rats induced by administration of trimethyltin (TMT), an organotin compound that is neurotoxic to these animals. The ability of WO to improve cognitive efficacy in the TMT-induced neurodegenerative rats was investigated using a passive avoidance test, and the Morris water maze test, and using immunohistochemistry to detect components of the acetylcholinergic system, brain-derived neurotrophic factor (BDNF), and cAMP-response element-binding protein (CREB) expression. Rats injected with TMT showed impairments in learning and memory and daily administration of WO improved memory function, and reduced aggressive behavior. Administration of WO significantly alleviated the TMT-induced loss of cholinergic immunoreactivity and restored the hippocampal expression levels of BDNF and CREB proteins and their encoding mRNAs to normal levels. These findings suggest that WO might be useful as a new therapy for treatment of various neurodegenerative diseases.

Identification of Amino Acid Residues Involved in the Interaction between Measles Virus Haemagglutin (MVH) and Its Human Cell Receptor(Signaling Lymphocyte Activation Molecule, SLAM)

  • Xu, Qin;Zhang, Peng;Hu, Chunling;Liu, Xin;Qi, Yipeng;Liu, Yingle
    • BMB Reports
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    • v.39 no.4
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    • pp.406-411
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    • 2006
  • Signaling lymphocyte activation molecule (SLAM; also known as CD150) is a newly identified cellular receptor for measles virus (MV). The interaction between MV Haemagglutin (MVH) and SLAM is an initial step for MV entry. We have identified several novel SLAM binding sites at residues S429, T436 and H437 of MVH protein and MVH mutants in these residues dramatically decrease the ability to interaction with the cell surface SLAM and fail to co-precipitation with SLAM in vivo as well as malfunction in syncytium formation. At the same time, K58, S59 and H61 of SLAM was also identified to be critical for MVH and SLAM binding. Further, these residues may be useful targets for the development of measles therapy.

Studies on Cadmium and Zinc Detoxification of Rumex maritimus (금소리쟁이(Rumex maritimus)의 카드뮴, 아연 내성에 관한 연구)

  • 김진희;이인숙
    • The Korean Journal of Ecology
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    • v.21 no.3
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    • pp.225-231
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    • 1998
  • The studies on the potentiality of biomonitoring heavy metal pollution in coastal region of industrial complex were performed to investigate the heavy metal accumulation and induction of metal-binding protein (MBP) as detoxification process using Rumex maritimus. Bioconcentration in organs and MBP in root of R. maritimus was investigated for the research of the tolerance of heavy metals. The bioconcentration of cadmium and zinc in organs showed 3.6-8.0 times in root higher than in shoot, so it was found that heavy metal accumulated selectively in root. MBP increased absorbance in 254 nm and decreased in 280 nm, because it was composed of high cystein content and low aromatic acids, so absorbance had large difference between 254 nm and 280 nm. The existence of MBP in the 10-20 fraction was ascertained with anion exchange chromatography and it was identified that concentration of heavy metal increased according as an exposure concentration of medium increased in QAE Sephadex A-25 elution profile. These results suggested that MBP could play a role in biomarker determining the bioconcentration of plant. This study demonstrated a possibility that removal ability of heavy metal of R. maritimus resulted from detoxification process and MBP could be utilized as a biomarker of heavy metal pollution.

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Screening and Purification of an Antimicrobial Peptide from the Gill of the Manila Clam Ruditapes philippinarum (바지락(Ruditapes philippinarum) 아가미로부터 항균 펩타이드의 탐색 및 정제)

  • Seo, Jung-Kil
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.49 no.2
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    • pp.137-145
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    • 2016
  • This study screened the biological activity of an acidified gill extract of the Manila clam Ruditapes philippinarum including antimicrobial, hemolytic, membrane permeabilization, and DNA-binding activity, and purified the antimicrobial material. The acidified gill extract showed potent antimicrobial activity against Bacillus subtilis and Escherichia coli without significant hemolytic activity, but showed no membrane permeabilization or DNA-binding ability. An antimicrobial material was purified from the acidified gill extract using C18 reversed-phase and cation-exchange high-performance liquid chromatography (HPLC). Treatment of the purified material with trypsin completely abolished all of the antibacterial activity against Bacillus subtilis, suggesting that the purified material is a proteinaceous antibiotic. The molecular weight of the purified material was 2571.9 Da, but no primary structural information was obtained due to N-terminal blocking. A future study should confirm the primary structure. Our results suggest that the Manila clam gill contains proteinaceous antibiotics that have a role in first-line defense. This information could be used to better understand the Manila clam innate immune system.

(A) Study on Natural Dyeing of polyester(I) - Ginseng Microcapsules - (폴리에스테르의 천연염색 처리 방법에 관한 연구(I) - 인삼 마이크로캡슐을 중심으로 -)

  • Min, Kyung-Hae
    • Fashion & Textile Research Journal
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    • v.10 no.4
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    • pp.560-565
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    • 2008
  • Plantae of the natural material has been broadly used on cloth dyeing by it's specific properties such as eco-friendly and innoxious. However dyeing with natural material on synthetic fiber is nearly impossible due to poor affinity between natural material and synthetic fiber. The method which is binding with micro-capsulized natural material to cloth, used in this study, has low change on quality by external influence. Also this method has high ability in spray effect by broken capsule which comes to pressure and friction when the treated cloth was dressed. And this method is applicable widely from natural fiber to synthetic fiber. The purpose of this study is to develop the multi-functional synthetic material with micro-capsulized Ginseng on PET. Moreover, it was driven by comparison of colormetric properties and fastness between regular dip-dyeing method and binding with micro-capsulized material method. Dyeability showed a little bit low exhaustion but the PET treated by micro-capsule was more or less better than the dip dyed PET. Through the SEM(Scanning Electron Microscope) of PET treated by micro-capsule, it has good residence of capsules even after 5 or 10 times washing. Wash and light fastness were revealed some different grades by each condition but showed high level, in most and the micro-capsulized PET was more improver than regular dip dyed PET.

Explorations of the Electrostatic Character of a Model of Human Immunodeficiency Virus Type 1 Integrase to Offer a Prediction for the Orientation and Nature of DNA binding

  • Jung, Eun-Sun;Kwon, Yong-Jung
    • Journal of Industrial Technology
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    • v.26 no.B
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    • pp.163-171
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    • 2006
  • Human immunodeficiency virus type 1 (HIV-1) integrase plays a critical role in the life cycle of the HIV virus. An ability to accurately map its electrostatic potential, and then use this information to predict the manner in which DNA will bind to the active site of the catalytic domain could provide a foundation for inhibitory design. Attempts to discern the crystal structure of HIV-1 integrase have proven problematic, especially in the region of enzymatic activity, that being those residues involved in the catalysis of the integration of viral DNA into the host cell. However, there is a structural correlation in to the region of interest with avian sarcoma virus (ASV), so a homology model utilizing this similarity was constructed to approximate the behavior/structure of the undetermined portions of the HIV-1 integrase crystal. After this model was constructed and its energy minimized, electrostatic calculations were carried out on the substance, so that an electrostatic potential map was constructed. Using this information, it was determined that DNA binding was oriented so as to exploit the regions of positive potential nearby the active site, as well as the positive potential of the magnesium cofactors.

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Non-classical role of Galectin-3 in cancer progression: translocation to nucleus by carbohydrate-recognition independent manner

  • Kim, Seok-Jun;Chun, Kyung-Hee
    • BMB Reports
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    • v.53 no.4
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    • pp.173-180
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    • 2020
  • Galectin-3 is a carbohydrate-binding protein and regulates diverse functions, including cell proliferation and differentiation, mRNA splicing, apoptosis induction, immune surveillance and inflammation, cell adhesion, angiogenesis, and cancer-cell metastasis. Galectin-3 is also recommended as a diagnostic or prognostic biomarker of various diseases, including heart disease, kidney disease, and cancer. Galectin-3 exists as a cytosol, is secreted in extracellular spaces on cells, and is also detected in nuclei. It has been found that galectin-3 has different functions in cellular localization: (i) Extracellular galectin-3 mediates cell attachment and detachment. (ii) cytosolic galectin-3 regulates cell survival by blocking the intrinsic apoptotic pathway, and (iii) nuclear galectin-3 supports the ability of the transcriptional factor for target gene expression. In this review, we focused on the role of galectin-3 on translocation from cytosol to nucleus, because it happens in a way independent of carbohydrate recognition and accelerates cancer progression. We also suggested here that intracellular galecin-3 could be a potent therapeutic target in cancer therapy.

Comparison of Photocyclization Reactions of Fluoro- vs Nonfluoro-Substituted Polymethyleneoxy Donor Linked Phthalimides

  • Park, Hea Jung;Ryu, Young Ju;Kim, Kyung Mok;Yoon, Ung Chan;Kim, Eunae;Sohn, Youngku;Cho, Dae Won;Mariano, Patrick S.
    • Bulletin of the Korean Chemical Society
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    • v.34 no.4
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    • pp.1108-1114
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    • 2013
  • Photochemical reactions of fluoro- vs. nonfluoro-substituted polymethylenoxy chain linked phthalimide were carried out to explore how electronegative fluorine atoms inside the donor chain influence photocyclization reaction efficiencies and to briefly determine the alkali metal binding properties of the photoproducts. The results of this study show that the fluorine-substituted donor chain linked phthalimide undergoes inefficient photocyclization via single electron transfer (SET)-induced excited state pathways to generate 14-membered cyclic amidol compared to nonfluoro-analog due to low electron donor ability of the terminal oxygen donor site. These results show that photoinduced intramolecular SET processes arising from ${\alpha}$-silyl ether electron donors to phthalimides are largely dependent on the kinds of substituents inside donor chain. Finally, a preliminary study with the cyclic amidols generated in this effort showed that they have weak alkali metal cation binding properties regardless of absence/presence of fluoro-substituents.