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Li X.,University of Minnesota | Li X.,Zhengzhou University | Li H.,University of Minnesota | Li S.,University of Minnesota | And 19 more authors.
Carcinogenesis | Year: 2012

Ceftriaxone, an FDA-approved third-generation cephalosporin antibiotic, has antimicrobial activity against both gram-positive and gram-negative organisms. Generally, ceftriaxone is used for a variety of infections such as community-acquired pneumonia, meningitis and gonorrhea. Its primary molecular targets are the penicillin-binding proteins. However, other activities of ceftriaxone remain unknown. Herein, we report for the first time that ceftriaxone has antitumor activity in vitro and in vivo. Kinase profiling results predicted that Aurora B might be a potential 'off' target of ceftriaxone. Pull-down assay data confirmed that ceftriaxone could bind with Aurora B in vitro and in A549 cells. Furthermore, ceftriaxone (500 μM) suppressed anchorage-independent cell growth by targeting Aurora B in A549, H520 and H1650 lung cancer cells. Importantly, in vivo xenograft animal model results showed that ceftriaxone effectively suppressed A549 and H520 lung tumor growth by inhibiting Aurora B. These data suggest the anticancer efficacy of ceftriaxone for the treatment of lung cancers through its inhibition of Aurora B. © The Author 2012. Published by Oxford University Press. All rights reserved.


Moon H.-D.,Chonnam National University | Lee M.-S.,Chonnam National University | Kim S.-H.,Chonnam National University | Jeong W.-J.,Korea Research Institute of Biosciences and Biotechnology | Choi D.-W.,Chonnam National University
Biologia Plantarum | Year: 2016

Plants have developed adaptive strategies to survive under different abiotic stressors. To identify new components involved in abiotic stress tolerance, we screened unannotated expressed sequence tags (ESTs) and evaluated their cold or drought response in Arabidopsis. We identified a drought response gene (DRG) encoding a 39.5-kDa polypeptide. This protein was expressed specifically in siliques and was induced by drought stress in most tissues. When a DRG-GFP construct was introduced into Arabidopsis protoplasts, GFP signals were detected only in the nucleus. The drg mutant plant was more sensitive to mannitol-induced osmotic stress in agar plates and to drought or freezing stress in soil than the wild-type. Activating the DRG restored the normal sensitivity of drg mutants to abiotic stressors. No differences in drought or freezing tolerance were observed between the wild-type and transgenic plants overexpressing the DRG. When DRG was expressed in a cold-sensitive Escherichia coli strain BX04, the transformed bacteria grew faster than the untransformed BXO4 cells under cold stress. These results demonstrate that DRG is a nuclear protein induced by abiotic stresses and it is required for drought and freezing tolerance in Arabidopsis. © 2016, Springer Science+Business Media Dordrecht.


Seo J.-S.,Seonam University | Choi J.-H.,Chonnam National University | Seo J.-H.,Chonnam National University | Ahn T.-H.,Seonam University | And 4 more authors.
Fisheries and Aquatic Science | Year: 2013

To determine the relative importance of two main factors, diet or culture environment, that affect the proximate composition and main nutritive ingredients (vitamin A, vitamin E, cholesterol, fatty acid composition) in cultured eels, we analyzed the composition of eels fed diets of formula feed (FF) produced by four different companies and of eels cultured at five different eel farms that provided only one of the four different FFs. The four commercial eel FFs did not markedly differ in proximate composition or major nutritive compounds, and consequently, these variables did not significantly differ in cultured eels fed the different FFs. The FF imported from Japan was marginally superior to the two domestic commercial FFs and the FF imported from Taiwan in terms of the proximate composition and main nutritive ingredients of both the FF itself and the eels cultured on it. However, proximate composition and main nutritive ingredients significantly differed among eels cultured at the five farms that used a different FF and among eels fed the four different FFs at the same farm. In conclusion, the difference in quality between domestic and Japanese FFs in terms of eel culture was small, whereas physical or chemical environmental differences among farms during eel culture may more strongly affect the proximate composition and levels of the main nutritive ingredients in cultured eels. © The Korean Society of Fisheries and Aquatic Science.


Dumbrepatil A.B.,Chungbuk National University | Dumbrepatil A.B.,Korea Research Institute of Biosciences and Biotechnology | Choi J.-H.,Seoul National University | Choi J.-H.,Inje University | And 7 more authors.
Proteins: Structure, Function and Bioinformatics | Year: 2010

The debranching enzyme Nostoc punctiforme debranching enzyme (NPDE) from the cyanobacterium Nostoc punctiforme (PCC73102) hydrolyzes the α-1,6 glycosidic linkages of malto-oligosaccharides. Despite its high homology to cyclodextrin/pullulan (CD/PUL)-hydrolyzing enzymes from glycosyl hydrolase 13 family (GH-13), NPDE exhibits a unique catalytic preference for longer malto-oligosaccharides (>G8), performing hydrolysis without the transgylcosylation or CDhydrolyzing activities of other GH-13 enzymes. To investigate the molecular basis for the property of NPDE, we determined the structure of NPDE at 2.37-Å resolution. NPDE lacks the typical N-terminal domain of other CD/PUL-hydrolyzing enzymes and forms an elongated dimer in a head-to-head configuration. The unique orientation of residues 25-55 in NPDE yields an extended substrate binding groove from the catalytic center to the dimeric interface. The substrate binding groove with a lengthy cavity beyond the -1 subsite exhibits a suitable architecture for binding longer malto-oligosaccharides (>G8). These structural results may provide a molecular basis for the substrate specificity and catalytic function of this cyanobacterial enzyme, distinguishing it from the classical neopullulanases and CD/PUL-hydrolyzing enzymes. © 2009 Wiley-Liss, Inc.


Lee K.,Dongguk University | Cho S.H.,Chungnam National University | Lee J.H.,Chungnam National University | Goo J.,Korea University | And 8 more authors.
European Journal of Medicinal Chemistry | Year: 2013

We report a new series of naphthoquinone derivatives as potent ACAT inhibitors, which were obtained through structural variations of previously disclosed lead 1. Several analogs represented by 3i-l, 4k-m, 6a-n, 7a, and 7i demonstrated potent human macrophage ACAT inhibitory activity by a cell-based reporter assay with human HepG2 cell lines. In particular, compounds 4l and 6j emerged as highly potent inhibitors, exhibiting significantly high inhibitory potencies with IC50 values of 0.44 μM and 0.6 μM, respectively. Moreover, compound 4l significantly reduced the accumulation of cellular cholesterol in HepG2 cell lines. © 2012 Elsevier Masson SAS. All rights reserved.


Jeong Y.-S.,Korea Advanced Institute of Science and Technology | Choi S.-L.,Korea Research Institute of Biosciences and Biotechnology | Kyeong H.-H.,Korea Advanced Institute of Science and Technology | Kim J.-H.,Korea Advanced Institute of Science and Technology | And 6 more authors.
Protein Engineering, Design and Selection | Year: 2012

Synthetic organophosphates (OPs) have been used as nerve agents and pesticides due to their extreme toxicity and have caused serious environmental and human health problems. Hence, effective methods for detoxification and decontamination of OPs are of great significance. Here we constructed and used a high-throughput screening (HTS) system that was based on phenolics-responsive transcription activator for directed evolution of OP-degrading enzymes. In the screening system, phenolic compounds produced from substrates by OP-degrading enzymes bind a constitutively expressed transcription factor DmpR, initiating the expression of enhanced green fluorescent protein located at the downstream of the DmpR promoter. Fluorescence intensities of host cells are proportional to the levels of phenolic compounds, enabling the screening of OP-degrading enzymes with high catalytic activities by fluorescence-activated cell sorting. Methyl parathion hydrolase from Pseudomonas sp. WBC-3 and p-nitrophenyl diphenylphosphate were used as a model enzyme and an analogue of G-type nerve agents, respectively. The utility of the screening system was demonstrated by generating a triple mutant with a 100-fold higher kcat/Km than the wild-type enzyme after three rounds of directed evolution. The contributions of individual mutations to the catalytic efficiency were elucidated by mutational and structural analyses. The DmpR-based screening system is expected to be widely used for developing OP-degrading enzymes with greater potential. © 2012 The Author.


Dumbrepatil A.,Chungbuk National University | Dumbrepatil A.,Korea Research Institute of Biosciences and Biotechnology | Park J.-M.,Chungbuk National University | Jung T.Y.,Korea Research Institute of Biosciences and Biotechnology | And 6 more authors.
Journal of Microbiology and Biotechnology | Year: 2012

An α-L-arabinofuranosidase (TmAFase) from Thermotoga maritima MSB8 is a highly thermostable exo-acting hemicellulase that exhibits a relatively higher activity towards arabinan and arabinoxylan, compared with other glycoside hydrolase 51 family enzymes. In the present study, we carried out the enzymatic characterization and structural analysis of TmAFase. Tight domain associations found in TmAFase, such as an inter-domain disulfide bond (Cys306 and Cys476) in each monomer, a novel extended arm (amino acids 374-385) at the dimer interface, and total 12 salt bridges in the hexamer, may account for the thermostability of the enzyme. One of the xylan binding determinants (Trp96) was identified in the active site, and a region of amino acids (374-385) protrudes out forming an obvious wall at the substrate-binding groove to generate a cavity. The altered cavity shape with a strong negative electrostatic distribution is likely related to the unique substrate preference of TmAFase towards branched polymeric substrates. © The Korean Society for Microbiology and Biotechnology.


Choudhary R.K.,Korea Research Institute of Biosciences and Biotechnology
Genetics and molecular research : GMR | Year: 2012

The nuclear ribosomal DNA internal transcribed spacer (ITS) sequences from 44 Indian Polygonum taxa were examined to investigate relationships among various sections proposed by earlier researchers. The maximum parsimony trees obtained from analysis of the ITS sequences suggested eight major groups of the Indian Polygonum spp. The relationships among different sections were largely congruent with those inferred from morphological characters as described by Hooker. Also, the treatment of the Persicaria suggested by Haraldson on the basis of anatomical characters proved to be nearly in line with that based on our molecular data. We provide a high resolution of phylogeny of the Himalayan Polygonum sensu lato and support merger of the section Amblygonon in the section Persicaria. Moreover, we made the first phylogenetic analysis of many of the less known Himalayan Polygonums, including Polygonum microcephalum, P. assamicum, P. recumbens, and P. effusum. Molecular differences were detected among Persicaria barbata collected from different geographical locations of India, although these were not differentiated at the morphological level.


PubMed | Korea Research Institute of Biosciences and Biotechnology
Type: Journal Article | Journal: Genetics and molecular research : GMR | Year: 2013

The nuclear ribosomal DNA internal transcribed spacer (ITS) sequences from 44 Indian Polygonum taxa were examined to investigate relationships among various sections proposed by earlier researchers. The maximum parsimony trees obtained from analysis of the ITS sequences suggested eight major groups of the Indian Polygonum spp. The relationships among different sections were largely congruent with those inferred from morphological characters as described by Hooker. Also, the treatment of the Persicaria suggested by Haraldson on the basis of anatomical characters proved to be nearly in line with that based on our molecular data. We provide a high resolution of phylogeny of the Himalayan Polygonum sensu lato and support merger of the section Amblygonon in the section Persicaria. Moreover, we made the first phylogenetic analysis of many of the less known Himalayan Polygonums, including Polygonum microcephalum, P. assamicum, P. recumbens, and P. effusum. Molecular differences were detected among Persicaria barbata collected from different geographical locations of India, although these were not differentiated at the morphological level.

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