• BMB Reports
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• v.51 no.8
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• pp.388-393
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• 2018

The activating transcription factor (ATF) 4 belongs to the ATF/CREB (cAMP Response Element Binding bZIP [Basic Leucine Zipper]) transcription factor family, and plays a central role in the UPR (Unfolded Protein Response) process in cells. The induction of ATF4 expression has previously been shown to increase the replication of HIV-1. However, the detailed mechanism underlying this effect and the factors involved in the regulation of ATF4 function are still unknown. Here, we demonstrate first that knocking out ATF4 using siRNA shows a strong negative effect on HIV-1 production, indicating that ATF4 is a functional positive cellular factor in HIV-1 production. To determine the mechanism by which ATF4 regulates the HIV-1 life cycle, we assessed the effect of the overexpression of wild type ATF4 and its various derivatives on HIV-1 LTR-mediated transcriptional activation and the production of HIV-1 particles. This effect was studied through co-transfection experiments with either reporter vectors or proviral DNA. We found that the N-terminal domains of ATF4 are involved in HIV-1 LTR-mediated transcriptional activation, and thus in HIV-1 production.

• Journal of Pharmacopuncture
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• v.18 no.3
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• pp.32-41
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• 2015

Objectives: Condurango (Gonolobus condurango) extract is used by complementary and alternative medicine (CAM) practitioners as a traditional medicine, including homeopathy, mainly for the treatment of syphilis. Condurango bark extract is also known to reduce tumor volume, but the underlying molecular mechanisms still remain unclear. Methods: Using a cervical cancer cell line (HeLa) as our model, the molecular events behind condurango extract's (CE's) anticancer effect were investigated by using flow cytometry, immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR). Other included cell types were prostate cancer cells (PC3), transformed liver cells (WRL-68), and peripheral blood mononuclear cells (PBMCs). Results: Condurango extract (CE) was found to be cytotoxic against target cells, and this was significantly deactivated in the presence of N-acetyl cysteine (NAC), a scavenger of reactive oxygen species (ROS), suggesting that its action could be mediated through ROS generation. CE caused an increase in the HeLa cell population containing deoxyribonucleic acid (DNA) damage at the G zero/Growth 1 (G0/G1) stage. Further, CE increased the tumor necrosis factor alpha ($TNF-{\alpha}$) and the fas receptor (FasR) levels both at the ribonucleic acid (RNA) and the protein levels, indicating that CE might have a cytotoxic mechanism of action. CE also triggered a sharp decrease in the expression of nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) both at the RNA and the protein levels, a possible route to attenuation of B-cell lymphoma 2 (Bcl-2), and caused an opening of the mitochondrial membrane's permeability transition (MPT) pores, thus enhancing caspase activities. Conclusion: Overall, our results suggest possible pathways for CE mediated cytotoxicity in model cancer cells.

• BMB Reports
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• v.29 no.3
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• pp.210-214
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• 1996

The pH dependence of the kinetic parameters of mutant O-acetylserine sulfhydrylase (OASS) from Salmonella typhimurium LT-2 has been determined in order to obtain information on the chemical mechanism. The initial velocity pattern obtained by varying the concentrations of OAS at several fixed concentrations of TNB, shows an intersection on the left of the ordinate at pH 7.0, indicating that the kinetic mechanism is a sequential mechanism in which substrate inhibition by OAS is observed while the wild type enzyme showed a ping pong mechanism. The values of $V/E_t$, $V/K_{OAS}E_{t}$ and $V/K_{TNB}E_{t}$ decreased by about 68%, 14% and 16% as compared with the wild type enzyme. The $V/K_{OAS}E_{t}$ is a pK of 6.5 on the acid side of the pH profile, and the $V/K_{TNB}$ is pH independent. As compared with the wild type enzyme, the pKs in the V/K profiles are shifted, reflecting that binding of the cofactor in free E:OAS is less asymmetric.

• Proceeding of EDISON Challenge
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• 2014.03a
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• pp.141-155
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• 2014

Peptide bond hydrolysis는 세포 내외의 생화학반응에 있어서 핵심이다. 하지만 amide Hydrolysis Mechanism은 아직 명확하게 규명되지 않았다. pH가 중성인 물에서의 비 촉매 가수분해가 발생하는 몇몇 실험적 증거가 있지만, 해당 반응 매커니즘은 4 가지(non-assisted concerted, non-assisted step-wise, assisted concerted, assisted step-wise)로 여전히 논란이 있다. 이번 연구에서는, Formamide의 가능한 Hydrolysis Mechanism을 자세히 연구해보고자 한다. 먼저, Ab-initio 계산을 통해 4가지 반응 메커니즘의 다시 한번 확인하고, quantum chemical calculations과 quantum mechanical molecular dynamic이 결합된 (QMMD) simulation을 통하여 water solvent에서의 반응 메커니즘의 에너지관계를 규명하였다. 결론적으로 아직 계산이 끝나지 않은 supported concerted mechanism을 제외한 모든 계산에서 non-supported, supported 두 system 모두에서 step-wise가 일어나기 쉬웠고, non-supported 보다 supported mechanism이 선호됨을 보였다. Intermediate인 amino-gem-diol의 수용액 상에서 안정화 또한 나타났다. 이는 Ab-initio 계산만 통해서는 정확하게 산출할 수 없는 엔트로피의 영향을 잘 보여준다.

• BMB Reports
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• v.52 no.7
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• pp.424-433
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• 2019

Autism spectrum disorder (ASD) is a complex neurodevelopmental monogenic disorder with a strong genetic influence. Idiopathic autism could be defined as a type of autism that does not have a specific causative agent. Among signalling cascades, mTOR signalling pathway plays a pivotal role not only in cell cycle, but also in protein synthesis and regulation of brain homeostasis in ASD patients. The present review highlights, underlying mechanism of mTOR and its role in altered signalling cascades as a triggering factor in the onset of idiopathic autism. Further, this review discusses how distorted mTOR signalling pathway stimulates truncated translation in neuronal cells and leads to downregulation of protein synthesis at dendritic spines of the brain. This review concludes by suggesting downstream regulators such as p70S6K, eIF4B, eIF4E of mTOR signalling pathway as promising therapeutic targets for idiopathic autistic individuals.

• BMB Reports
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• v.38 no.3
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• pp.259-265
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• 2005

Proteins must fold into their correct three-dimensional conformation in order to attain their biological function. Conversely, protein aggregation and misfolding are primary contributors to many devastating human diseases, such as prion-mediated infections, Alzheimer's disease, type II diabetes and cystic fibrosis. While the native conformation of a polypeptide is encoded within its primary amino acid sequence and is sufficient for protein folding in vitro, the situation in vivo is more complex. Inside the cell, proteins are synthesized or folded continuously; a process that is greatly assisted by molecular chaperones. Molecular chaperones re a group of structurally diverse and mechanistically distinct proteins that either promote folding or prevent the aggregation of other proteins. With our increasing understanding of the proteome, it is becoming clear that the number of proteins that can be classified as molecular chaperones is increasing steadily. Many of these proteins have novel but essential cellular functions that differ from that of more 'conventional' chaperones, such as Hsp70 and the GroE system. This review focuses on the emerging role of molecular chaperones in protein quality control, i.e. the mechanism that rids the cell of misfolded or incompletely synthesized polypeptides that otherwise would interfere with normal cellular function.

• BMB Reports
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• v.30 no.2
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• pp.157-161
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• 1997

The present paper reports characteristics and specificity of the inhibitory action of $N^{\alpha}-tosyl-L-lysine-chloromethyl\;ketone$ (TLCK) and $N^{\alpha}-tosyl-L-phenylalanine-chloromethyl\;ketone$ (TPCK) on the glucose6-phosphate transporter of rat liver microsomes. The TLCK-induced inhibition was pH dependent. The inhibition constants for TPCK were determined by following pseudo-Lst order reaction mechanism. The inhibition was protected by preincubation with excess amount of glucose-6-phosphate. The results proved that (a) TLCK inactivates the microsomal glucose-6-phosphate transporter, (b) the inhibition results from the modification of sulfhydryl groups of the transporter.

• Proceedings of the KSME Conference
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• 2007.05a
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• pp.337-342
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• 2007

In this study, molecular dynamics simulation of nano imprint lithography in which patterned stamp is pressed onto amorphous polyethylene(PE) surface are performed to study the behaviour of polymer. Force fields including bond, angle, torsion, and Lennard Jones potential are used to describe the inter-molecular and intra-molecular force of PE molecules and stamp, substrate. Periodic boundary condition is used in horizontal direction and canonical NVT ensemble is used to control the system temperature. As the simulation results, the behaviour of polymer is investigated during the imprinting process. The mechanism of polymer deformation is studied by means of inspecting the surface shape, volume, density, atom distribution. Deformation of the polymer resist was found for various of the stamp geometry and the alignment state of the polymer molecules.

• CELLMED
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• v.6 no.4
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• pp.24.1-24.4
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• 2016

The emergence of influenza virus and antigenic drift are potential cause of world-wide pandemic. There are some commercially available drugs in the market to treat influenza. During past decade, however, critical resistances have been raised for biological targets. Because of structural complexity and flexibility of target proteins, applying a computational modeling tool is very beneficial for developing alternative anti-influenza drugs. In this review, we introduced molecular dynamics (MD) simulations approach to reflect full conformational flexibility of proteins during molecular modeling works. Case studies of MD works were summarized for the drug discovery and drug resistance mechanism of anti-influenza pharmaceuticals.

• Journal of the Korean Institute of Electrical and Electronic Material Engineers
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• v.11 no.4
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• pp.306-313
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• 1998

To elucidate the liquid crystal(LC) molecules alignment mechanism, it is important to determine the molecular orientation of the rubbed polymer surface molecules that directly contact with LC molecules. In this work, the molecular orientation on a rubbed surface of polyimide (SE-3310, Nissan) film has been studied by polarized FTIR absorption spectroscopy. It has been found that molecular chain on the rubbed surface of polymide film are oriented along the rubbing direction and are tilted up on an average by 5.0$^{\circ}$. In the SHG(Second Harmonic Generation) measurement, the pretilt angle of molecular chain on the poylmide fim was 4.6$^{\circ}$ fro, the surface plane. And the pedit angle of liquid crystal (ZLI-2293, Merck) molecules measured by crystal rotation method was 5.4$^{\circ}$in the same rubbing condition.