Korean BioInformation Center

Daejeon, South Korea

Korean BioInformation Center

Daejeon, South Korea

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Jung Y.,Ewha Research Center for Systems Biology | Jung Y.,Ewha Womans University | Kim P.,Ewha Research Center for Systems Biology | Kim P.,Ewha Womans University | And 16 more authors.
Genes Chromosomes and Cancer | Year: 2012

An increasing number of chromosomal aberrations is being identified in solid tumors providing novel biomarkers for various types of cancer and new insights into the mechanisms of carcinogenesis. We applied next generation sequencing technique to analyze the transcriptome of the non-small cell lung carcinoma (NSCLC) cell line H2228 and discovered a fusion transcript composed of multiple exons of ALK (anaplastic lymphoma receptor tyrosine kinase) and PTPN3 (protein tyrosine phosphatase, nonreceptor Type 3). Detailed analysis of the genomic structure revealed that a portion of genomic region encompassing Exons 10 and 11 of ALK has been translocated into the intronic region between Exons 2 and 3 of PTPN3. The key net result appears to be the null mutation of one allele of PTPN3, a gene with tumor suppressor activity. Consistently, ectopic expression of PTPN3 in NSCLC cell lines led to inhibition of colony formation. Our study confirms the utility of next generation sequencing as a tool for the discovery of somatic mutations and has led to the identification of a novel mutation in NSCLC that may be of diagnostic, prognostic, and therapeutic importance. © 2012 Wiley Periodicals, Inc.


PubMed | Kyungpook National University, Korean Bioinformation Center, Catholic University of Daegu and Food Republic
Type: Journal Article | Journal: Bioorganic & medicinal chemistry | Year: 2015

Three new serratene-type triterpenoids (1-3) and a new hydroxy unsaturated fatty acid (13) together with nine known compounds (4-12) were isolated from Lycopodiella cernua. The chemical structures were established using NMR, MS, and Moshers method. Compound 13 showed the most potent inhibitory activity against acetylcholinesterase (AChE) with an IC50 value of 0.22M. For butyrylcholinesterase (BChE) inhibitory activity, 5 showed the most potent activity with an IC50 value of 0.42M. Compound 2 showed the most potent activity with an IC50 of 0.23M for BACE-1 inhibitory activity. The kinetic activities were investigated to determine the type of enzyme inhibition involved. The types of AChE inhibition shown by compounds 4, 5, and 13 were mixed; BChE inhibition by 5 was competitive, while 2 and 6 showed mixed-types. In addition, molecular docking studies were performed to investigate the interaction of these compounds with the pocket sites of AChE. The docking results revealed that the tested inhibitors 3, 4, and 13 were stably present in several pocket domains of the AChE residue.


PubMed | Pukyong National University, Kyungpook National University, Korean BioInformation Center, Catholic University of Daegu and iMinh City University of Medicine and Pharmacy
Type: | Journal: Chemico-biological interactions | Year: 2015

Acetylcholinesterase (AChE) inhibitors increase the availability of acetylcholine in central cholinergic synapses and are the most promising drugs currently available for the treatment of Alzheimers disease (AD). Our screening study indicated that the water fraction of the methanolic extract of Lycopodiella cernua (L.) Pic. Serm. significantly inhibited AChE invitro. Bioassay-guided fractionation led to the isolation of a new lignan glycoside, lycocernuaside A (12), and fourteen known compounds (1-11 and 13-15). Compound 7 exhibited the most potent AChE inhibitory activity with an IC50 value of 0.23M. Compound 15 had the most potent inhibitory activity against BChE and BACE1 with IC50 values of 0.62 and 2.16M, respectively. Compounds 4 and 7 showed mixed- and competitive-type AChE inhibition. Compound 7 noncompetitively inhibited BChE whereas 15 showed competitive and 8, 13, and 14 showed mixed-type inhibition. The docking results for complexes with AChE or BChE revealed that inhibitors 4, 7, and 15 stably positioned themselves in several pocket/catalytic domains of the AChE and BChE residues.


Cho S.,Ewha Womans University | Jun Y.,Ewha Womans University | Lee S.,Ewha Womans University | Choi H.-S.,Ewha Womans University | And 6 more authors.
Nucleic Acids Research | Year: 2011

MiRGator is an integrated database of microRNA (miRNA)-associated gene expression, target prediction, disease association and genomic annotation, which aims to facilitate functional investigation of miRNAs. The recent version of miRGator v2.0 contains information about (i) human miRNA expression profiles under various experimental conditions, (ii) paired expression profiles of both mRNAs and miRNAs, (iii) gene expression profiles under miRNA-perturbation (e.g. miRNA knockout and overexpression), (iv) known/predicted miRNA targets and (v) miRNA-disease associations. In total, >8000 miRNA expression profiles, ̃300 miRNA-perturbed gene expression profiles and ̃2000 mRNA expression profiles are compiled with manually curated annotations on disease, tissue type and perturbation. By integrating these data sets, a series of novel associations (miRNA-miRNA, miRNA-disease and miRNA-target) is extracted via shared features. For example, differentially expressed genes (DEGs) after miRNA knockout were systematically compared against miRNA targets. Likewise, differentially expressed miRNAs (DEmiRs) were compared with disease-associated miRNAs. Additionally, miRNA expression and disease-phenotype profiles revealed miRNA pairs whose expression was regulated in parallel in various experimental and disease conditions. Complex associations are readily accessible using an interactive network visualization interface. The miRGator v2.0 serves as a reference database to investigate miRNA expression and function (http://miRGator.kobic.re.kr). © The Author(s) 2010.


Jung H.A.,Chonbuk National University | Cho Y.S.,Korea University | Oh S.H.,Korean BioInformation Center | Lee S.,Korean BioInformation Center | And 4 more authors.
Archives of Pharmacal Research | Year: 2013

Since insulin sensitivity to cells is attributed to phosphorylation of the insulin receptor (IR), protein tyrosine phosphatase 1B (PTP1B), which dephosphorylates the tyrosine residues of IR proteins, is primarily responsible for insulin resistance in type 2 diabetes. Therefore, PTP1B inhibitors ameliorating the insulin-dependent signaling pathway are potential therapeutic candidates for the treatment and prevention of diabetes. As part of our continuous search for diterpenes derived from Aralia continentalis as potent PTP1B inhibitors, five active diterpenoids, including ent-pimara-8(14),15-diene- 19-oic acid (1); 7-oxo-ent-pimara-8(14),15-diene-19-oic acid (2); 7β-hydroxy-ent-pimara-8(14),15-diene-19-oic acid (3); ent-pimara-8(14),15- diene-19-ol (4); 8α-hydroxy-ent-pimara-15-en-19-ol (5); and ent-kaur-16-en-19-oic-acid (6) were investigated using the enzyme kinetic assay. With the exception of 1 showing mixed inhibition, compounds 2 and 4-6 exhibited noncompetitive inhibition against PTP1B with K i values ranging 3.29-12.86 μM. In particular, 2 with an oxo group in the C-7 position showed increased PTP1B inhibition compared to nonsubstituted 1. Based on the structure and activity relationship, the 3D docking simulations of 1, 2, and 3 were also performed. Compounds 1-3 showed negative binding energies of -5.3 to -6.1 kcal/mol and a high affinity to PTP1B residues (Phe182 and Asp181 in the WPD loop; Cys215 in the active sites; Tyr46, Arg47, Asp48, Val49, Ser216, Ala217, Gly218, Ile219, Gly220, Arg221, Gln262, and Gln266 in the pocket site), indicating that they may stabilize the open form and generate tighter binding to the catalytic sites of PTP1B. The enzymatic kinetics and docking results clearly indicate the promising potential of pimarane-type diterpenes as PTP1B inhibitors. © 2013 The Pharmaceutical Society of Korea.


Jung H.A.,Pukyong National University | Oh S.H.,Korean BioInformation Center | Choi J.S.,Pukyong National University | Choi J.S.,Dong - Eui University
Bioorganic and Medicinal Chemistry Letters | Year: 2010

In our consecutive research on an anti-AD remedy derived from maritime plants, the BACE1 inhibitory activities of Eisenia bicyclis and its isolated phlorotannins were evaluated. The E. bicyclis extract and its fractions exhibited predominant BACE1 inhibition. With the exception of phloroglucinol (1), all test phlorotannins isolated from the most active EtOAc soluble fraction, showed significant and non-competitive inhibition against BACE1:dioxinodehydroeckol (2, IC50 = 5.35 μM; Ki = 8.0); eckol (3, IC50 = 12.20 μM; Ki = 13.9); phlorofurofucoeckol-A (4, IC50 = 2.13 μM; Ki = 1.3); dieckol (5, IC50 = 2.21 μM; Ki = 1.5); triphloroethol A (6, IC50 = 11.68 μM; Ki = 12.1); 7-phloroethol (7, IC50 = 8.59 μM; Ki = 7.2). In addition, plausible protein-ligand interactions of 3, 4, and 5 were similar and may occur primarily through the TYR132 and THR133 of BACE1 via molecular docking simulations (autodock 4.0 and fred 2.0 programs). As a result, the E. bicyclis extract and the phlorotannins contained therein would clearly have beneficial use in the development of therapeutic and preventive agents for AD and suggest potential guidelines for the design of BACE-selective inhibitors. © 2010 Elsevier Ltd. All rights reserved.


Choi J.S.,Pukyong National University | Ali M.Y.,Pukyong National University | Jung H.A.,Chonbuk National University | Oh S.H.,Korean BioInformation Center | And 2 more authors.
Journal of Ethnopharmacology | Year: 2015

Ethnopharmacologic relevance: Rhizoma Coptidis (the rhizome of Coptis chinensis Franch) has commonly been used for treatment of diabetes mellitus in traditional Chinese medicine due to its blood sugarlowering properties and therapeutic benefits which highly related to the alkaloids therein. However, a limited number of studies focused on the Coptis alkaloids other than berberine. Materials and methods: In the present study, we investigated the anti-diabetic potential of Coptis alkaloids, including berberine (1), epiberberine (2), magnoflorine (3), and coptisine (4), by evaluating the ability of these compounds to inhibit protein tyrosine phosphatase 1B (PTP1B), and ONOO--mediated protein tyrosine nitration. We scrutinized the potentials of Coptis alkaloids as PTP1B inhibitors via enzyme kinetics and molecular docking simulation. Results: The Coptis alkaloids 1-4 exhibited remarkable inhibitory activities against PTP1B with the IC50 values of 16.43, 24.19, 28.14, and 51.04 μM, respectively, when compared to the positive control ursolic acid. These alkaloids also suppressed ONOO--mediated tyrosine nitration effectively in a dose dependent manner. In addition, our kinetic study using the Lineweaver-Burk and Dixon plots revealed that 1 and 2 showed a mixed-type inhibition against PTP1B, while 3 and 4 noncompetitively inhibited PTP1B. Moreover, molecular docking simulation of these compounds demonstrated negative binding energies (Autodock 4.0=-6.7 to -7.8 kcal/mol; Fred 2.0=-59.4 to -68.2 kcal/mol) and a high proximity to PTP1B residues, including Phe182 and Asp181 in the WPD loop, Cys215 in the active sites and Tyr46, Arg47, Asp48, Val49, Ser216, Ala217, Gly218, Ile219, Gly220, Arg221 and Gln262 in the pocket site, indicating a higher affinity and tighter binding capacity of these alkaloids for the active site of the enzyme. Conclusion: Our results clearly indicate the promising anti-diabetic potential of Coptis alkaloids as inhibitors on PTP1B as well as suppressors of ONOO--mediated protein tyrosine nitration, and thus hold promise as therapeutic agents for the treatment of diabetes and related disease. © 2015 Elsevier Ireland Ltd. All rights reserved.


PubMed | Pukyong National University, Korean BioInformation Center, Chonbuk National University and University of Cambridge
Type: | Journal: Journal of ethnopharmacology | Year: 2015

Rhizoma Coptidis (the rhizome of Coptis chinensis Franch) has commonly been used for treatment of diabetes mellitus in traditional Chinese medicine due to its blood sugar-lowering properties and therapeutic benefits which highly related to the alkaloids therein. However, a limited number of studies focused on the Coptis alkaloids other than berberine.In the present study, we investigated the anti-diabetic potential of Coptis alkaloids, including berberine (1), epiberberine (2), magnoflorine (3), and coptisine (4), by evaluating the ability of these compounds to inhibit protein tyrosine phosphatase 1B (PTP1B), and ONOO(-)-mediated protein tyrosine nitration. We scrutinized the potentials of Coptis alkaloids as PTP1B inhibitors via enzyme kinetics and molecular docking simulation.The Coptis alkaloids 1-4 exhibited remarkable inhibitory activities against PTP1B with the IC50 values of 16.43, 24.19, 28.14, and 51.04 M, respectively, when compared to the positive control ursolic acid. These alkaloids also suppressed ONOO(-)-mediated tyrosine nitration effectively in a dose dependent manner. In addition, our kinetic study using the Lineweaver-Burk and Dixon plots revealed that 1 and 2 showed a mixed-type inhibition against PTP1B, while 3 and 4 noncompetitively inhibited PTP1B. Moreover, molecular docking simulation of these compounds demonstrated negative binding energies (Autodock 4.0=-6.7 to -7.8 kcal/mol; Fred 2.0=-59.4 to -68.2 kcal/mol) and a high proximity to PTP1B residues, including Phe182 and Asp181 in the WPD loop, Cys215 in the active sites and Tyr46, Arg47, Asp48, Val49, Ser216, Ala217, Gly218, Ile219, Gly220, Arg221 and Gln262 in the pocket site, indicating a higher affinity and tighter binding capacity of these alkaloids for the active site of the enzyme.Our results clearly indicate the promising anti-diabetic potential of Coptis alkaloids as inhibitors on PTP1B as well as suppressors of ONOO(-)-mediated protein tyrosine nitration, and thus hold promise as therapeutic agents for the treatment of diabetes and related disease.


PubMed | Korean Bioinformation Center and sookeun@kribb.re.kr.
Type: Journal Article | Journal: Genome announcements | Year: 2015

Bacillus subtilis ATCC 6051a (=KCTC 1028), which is less domesticated than strain 168, is widely used for the secretory expression of industrial enzymes. Herein, we present the complete genome sequence of the Bacillus subtilis strain ATCC 6051a.


PubMed | Pukyong National University, Korean BioInformation Center, Mawlana Bhashani Science and Technology University, Chonbuk National University and University of Cambridge
Type: Journal Article | Journal: Archives of pharmacal research | Year: 2016

Caffeoylquinic acids, flavonoids, and coumarins isolated from Artemisia capillaris have recently emerged as therapeutic candidates for diabetes and diabetic complications; however, there have been very few studies of the anti-diabetic potential of polyacetylenes. In the present study, we investigated the anti-diabetic potential of two polyacetylenes isolated from A. capillaris, namely capillin and capillinol by investigating their ability to inhibit -glucosidase, protein tyrosine phosphatase 1B (PTP1B), and rat lens aldose reductase (RLAR). Capillin displayed potent inhibitory activity against -glucosidase, PTP1B, and RLAR, while capillinol showed moderate inhibitory activity against -glucosidase and PTP1B at the concentrations tested. In addition, a kinetic study revealed that capillin inhibited -glucosidase and RLAR in a noncompetitive manner, while inhibited PTP1B in a mixed-type manner. Capillinol inhibited -glucosidase and PTP1B in a mixed-type manner. Docking simulations of these compounds demonstrated negative binding energies and close proximity to residues in the binding pocket of PTP1B, indicating that these polyacetylenes have a high affinity and tight binding capacity for the active site of the enzyme. Furthermore, capillin dose-dependently inhibited peroxynitrite (ONOO(-))-mediated tyrosine nitration. The results clearly demonstrate the promising potential of capillin and capillinol as therapeutic interventions for the management of diabetes as well as diabetes-associated complications.

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