• Journal of Microbiology and Biotechnology
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• v.23 no.10
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• pp.1395-1402
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• 2013

Reductases convert some achiral ketone compounds into chiral alcohols, which are important materials for the synthesis of chiral drugs. The Saccharomyces cerevisiae reductase YOR120W converts ethyl-4-chloro-3-oxobutanoate (ECOB) enantioselectively into (R)-ethyl-4-chloro-3-hydroxybutanoate ((R)-ECHB), an intermediate of a pharmaceutical. As YOR120W requires NADPH as a cofactor for the reduction reaction, a cofactor recycling system using Bacillus subtilis glucose dehydrogenase was employed. Using this coupling reaction system, 100 mM ECOB was converted to (R)-ECHB. A homology modeling and site-directed mutagenesis experiment were performed to determine the NADPH-binding site of YOR120W. Four residues (Q29, K264, N267, and R270) were suggested by homology and docking modeling to interact directly with 2'-phosphate of NADPH. Among them, two positively charged residues (K264 and R270) were experimentally demonstrated to be necessary for NADPH 2'-phosphate binding. A mutant enzyme (Q29E) showed an enhanced enantiomeric excess value compared with that of the wild-type enzyme.

• Journal of Microbiology and Biotechnology
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• v.23 no.11
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• pp.1544-1553
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• 2013

Despite the importance of acetate kinase in the metabolism of bacteria, limited structural studies have been carried out on this enzyme. In this study, a three-dimensional structure of the Escherichia coli acetate kinase was constructed by use of molecular modeling methods. In the next stage, by considering the structure of the catalytic intermediate, trifluoroethanol (TFE) and trifluoroethyl butyrate were proposed as potential inhibitors of the enzyme. The putative binding mode of these compounds was studied with the use of a docking program, which revealed that they can fit well into the enzyme. To study the role of these potential enzyme inhibitors in the metabolic pathway of E. coli, their effects on the growth of this bacterium were studied. The results showed that growth was considerably reduced in the presence of these inhibitors. Changes in the profile of the metabolic products were studied by proton nuclear magnetic resonance spectroscopy. Remarkable changes were observed in the quantity of acetate, but other products were less altered. In this study, inhibition of growth by the two inhibitors as reflected by a change in the metabolism of E. coli suggests the potential use of these compounds (particularly TFE) as bacteriostatic agents.

• Journal of Microbiology and Biotechnology
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• v.23 no.11
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• pp.1529-1535
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• 2013

Tuberculosis is a worldwide epidemic disease caused by Mycobacterium tuberculosis, with an estimated one-third of the human population currently affected. Treatment of this disease with aminoglycoside antibiotics has become less effective owing to antibiotic resistance. Recent determination of the crystal structure of the M. tuberculosis Rv3168 protein suggests a structure similar to that of Enterococcus faecalis APH(3')-IIIa, and that this protein may be an aminoglycoside phosphotransferase. To determine whether Rv3168 confers antibiotic resistance against kanamycin, we performed dose-response antibiotic resistance experiments using kanamycin. Expression of the Rv3168 protein in Escherichia coli conferred antibiotic resistance against $100{\mu}M$ kanamycin, a concentration that effected cell growth arrest in the parental E. coli strain and an E. coli strain expressing the $Rv3168^{D249A}$ mutant, in which the catalytic Asp249 residue was mutated to alanine. Furthermore, we detected phosphotransferase activity of Rv3168 against kanamycin as a substrate. Moreover, docking simulation of kanamycin into the Rv3168 structure suggests that kanamycin fits well into the substrate binding pocket of the protein, and that the phosphorylation-hydroxyl-group of kanamycin was located at a position similar to that in E. faecalis APH(3')-IIIa. On the basis of these results, we suggest that the Rv3168 mediates kanamycin resistance in M. tuberculosis, likely through phosphotransferase targeting of kanamycin.

• Journal of Microbiology and Biotechnology
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• v.27 no.5
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• pp.878-895
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• 2017

Phosphorylation, a critical mechanism in biological systems, is estimated to be indispensable for about 30% of key biological activities, such as cell cycle progression, migration, and division. It is synergistically balanced by kinases and phosphatases, and any deviation from this balance leads to disease conditions. Pathway or biological activity-based abnormalities in phosphorylation and the type of involved phosphatase influence the outcome, and cause diverse diseases ranging from diabetes, rheumatoid arthritis, and numerous cancers. Protein tyrosine phosphatases (PTPs) are of prime importance in the process of dephosphorylation and catalyze several biological functions. Abnormal PTP activities are reported to result in several human diseases. Consequently, there is an increased demand for potential PTP inhibitory small molecules. Several strategies in structure-based drug designing techniques for potential inhibitory small molecules of PTPs have been explored along with traditional drug designing methods in order to overcome the hurdles in PTP inhibitor discovery. In this review, we discuss druggable PTPs and structure-based virtual screening efforts for successful PTP inhibitor design.

• YAKHAK HOEJI
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• v.54 no.4
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• pp.300-308
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• 2010

Adrenoceptor has been considered to be an important target in psychiatric disorders. Based on x-ray structures of bovine rhodopsin, we established homology model of ${\alpha}_{2c}$-adrenoceptor (ADA2C_rat) and then analyzed docking from binding model of receptor-ligand complex with high-active compound No.29 in tricyclic isoxazole analogues (1-30). We observed that the N (1.907 $\AA$) and O (1.712 $\AA$) atoms of isoxazole ring on the docked ligand (No.29) formed H-bonding interaction with O-H of Ser5.32 and carmeron phenyl ring centroid of tricyclic isoxazole formed $\pi-\pi$ interaction at 3.342 $\AA$ distance with phenyl ring centroid of Phe6.52. According to predictions of blood-brain distribution (logBB) through penetration of blood-brain barrie (BBB) and polar surface area (PSA) of the ligands, the high-active compound No.29 has values of logBB=-0.203, PSA=67.50, respectively. These results suggest that the high-active compound No.29 is a novel anti-depressant with the characteristics such as dopamine and serotonin.

• Proceedings of the KSR Conference
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• 2003.10b
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• pp.58-63
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• 2003

This study shows the functional contribution into the public transportation system for congestion area. And there is a introduction for the rapid bus transit developed in Europe community. It can be classified the public transportation as urban transit, subway and bus. For a few years, it has been introduced the AGT system as a role of the alternative and lengthening system of subway line. Recently, there is going on construction of AGT system in some regional cities. The AGT system has advantages in terms of accessibility and cost-effective rather than subway. But the bus system is advantageous at the points rather than AGT system. It is obvious that the bus system is most cost-effective for infrastructure and system rather than any other public transports. If the bus system has punctuality and precise docking, that becomes best choice for public transportation scheme. There are tries to develop new systems by means of the f1les up the advantages in bus and AGT system, which can be classified as BRT(Bus Rapid Transit}. The idea is simple; 'Thirik rail, use advanced buses.' It is introduced the IRISBUS system at this article, which was developed in Europe community. And it is introduced the project architecture to develop the similar system to IRISBUS in KRRI through National Transportation Key Technology R&D Project

• Journal of Integrative Natural Science
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• v.8 no.3
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• pp.164-175
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• 2015

CXCR3 is a C-X-C chemokine receptor type 3 also known as GPR9 and CD183. CXCR3 is a G-Protein coupled chemokine receptor which interacts with three endogenous interferon inducible chemokine's (CXCL9, CXCL10 and CXCL11) and is proved to play a vital role in the Th1 inflammatory responses. CXCR3 has been implicated to be associated with various disease conditions like inflammatory diseases, autoimmune diseases, type I diabetes and acute cardiac allograft rejection. Therefore CXCR3 receptor is found to be an attractive therapeutic target for the treatment of inflammatory diseases. Inorder to decipher the biological function of a CXCR3, 3D structure is of much important but the crystal structure for CXCR3 has not yet been resolved. Hence, in the current study Homology modeling of CXCR3 was performed against various templates and validated using different parameters to suggest the best model for CXCR3. The reported best model can be used for further studies such as docking to identify the important binding site residues.

• Journal of the military operations research society of Korea
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• v.32 no.2
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• pp.40-55
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• 2006

The objective of this paper is to provide an introductory scheme of Supply Chain Management(SCM) for the Air Force logistics support system. To accomplish our goal, we analyzed the successful example of the military logistics reform based on SCM in the United States, after we observed the concept and concerning methods of SCM. The introductory scheme of SCM was specifically provided on the transportation system and material information system of the aircraft repair parts, which are considered important in the Air Force logistics support system. The Air Force will be able to raise the complete mission supportability through the construction of an innovative logistics support system, which is low in cost and efficient, based on state of the art information and communication technology.

• Bulletin of the Korean Chemical Society
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• v.35 no.6
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• pp.1769-1776
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• 2014

Binding modes of a series of catechol derivatives such as protein tyrosine phosphatase 1B (PTP1B) inhibitors were identified by molecular modeling techniques. Docking, molecular dynamics simulations and free energy calculations were employed to determine the modes of these new inhibitors. Binding free energies were calculated by involving different energy components using the Molecular Mechanics-Poisson-Boltzmann Surface Area and Generalized Born Surface Area methods. Relatively larger binding energies were obtained for the catechol derivatives compared to one of the PTP1B inhibitors already in use. The Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) free energy decomposition analysis indicated that the hydroxyl functional groups and biphenyl ring system had favorable interactions with Met258, Tyr46, Gln262 and Phe182 residues of PTP1B. The results of hydrogen bound analysis indicated that catechol derivatives, in addition to hydrogen bonding interactions, Val49, Ile219, Gln266, Asp181 and amino acid residues of PTP1B are responsible for governing the inhibitor potency of the compounds. The information generated from the present study should be useful for the design of more potent PTP1B inhibitors as anti-diabetic agents.

• Bulletin of the Korean Chemical Society
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• v.28 no.7
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• pp.1151-1155
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• 2007

In a previous study, a catalyst (A) was discovered for oxidative decarboxylation of melanin-concentrating hormone (MCH). To explain the catalytic action and to predict the structure of a new catalyst with improved activity, docking simulations were carried out for the complex formed between A and MCH. The simulations suggested that the three terminal groups of A form a hydrophobic pocket and that van der Waals interactions between the hydrophobic pocket and MCH play a role in stabilizing the MCH-A complex. Consequently, a new catalyst (B) was designed and synthesized in expectation of improved catalytic activity resulting from enhanced van der Waals interactions. The new catalyst, however, showed slightly lower catalytic activity. Lack of the accurate solution structure of MCH may be one of the factors associated with difficulties in prediction of improvement in catalytic activity by purely theoretical means. The results, however, revealed that variation of the acyl portion of the hydroxyproline portion may lead to improved catalysts.