• 한국자기공명학회논문지
• /
• 제9권1호
• /
• pp.38-47
• /
• 2005

Axin is a scaffold protein of the APC/axin/GSK complex, binding to all of the other signalling components. Axin interacts with Glycogen synthase kinase 3$\beta$ (GSK 3$\beta$) and functions as a negative regulator of Wnt signalling pathways. To determine the solution structure of the GSK3$\beta$ binding regions of the axin, we initiated NMR study of axin fragment comprising residues 3$Val^{388} - Arg^{401}$using circular dichroism (CD) and two-dimensional NMR spectroscopy. The CD spectra of 3$axin^{pep}$ in the presence of 30% TFE displayed a standard 3$\alpha$-helical conformation, exhibiting the bound structure of 3$axin^{pep}$ to GSK3$\bata$. On the basis of experimental restraints including $NOE_s$, and $^3J_{HN\alpha} $ coupling constants, the solution conformation of $axin^{pep}$ was determined with program CNS. The 20 lowest energy structures were selected out of 50 final simulated-annealing structures in both water and TFE environment, respectively. The $RMSD_s$ for the 20 structures in TFE solution were 0.086 nm for backbone atoms and 0.195 nm for all heavy atoms, respectively. The Ramachandran plot indicates that the $\varphi$, $\psi$ angles of the 20 final structures is properly distributed in energetically acceptable regions. $Axin^pep$ in aqueous solutions consists of a stable $\alpha$-helix spanning residues form $Glu^{391}$ to $Val^{391} $, which is an interacting motif with GSK3$\beta$.

• ALGAE
• /
• 제30권2호
• /
• pp.163-170
• /
• 2015

Tyrosinase inhibitors are an important component of cosmetic products. Our previous studies have proposed that eckol isolated from the brown alga Ecklonia cava, can be explored as a tyrosinase inhibitor. However, cellular activities and mechanism of action of eckol remain unknown. Therefore, the current study analyzed the eckol binding modes using the crystal structure of Bacillus megaterium tyrosinase. The effects of eckol on melanin synthesis induced by ${\alpha}$-melanocyte stimulating hormone in B16F10 melanoma cells were also investigated. We predicted the 3D structure of tyrosinase and used a docking algorithm to simulate binding between tyrosinase and eckol. These molecular modeling studies were successful (calculated binding energy value, $-115.84kcal\;mol^{-1}$) and indicated that eckol interacts with Asn205, His208, and Arg209. Furthermore, eckol markedly inhibited tyrosinase activity and melanin synthesis in B16F10 melanoma cells. We also found that eckol decreased the expression of tyrosinase, tyrosinase-related protein (TRP) 1, and TRP2. These results indicate that eckol is a potent inhibitor of melanogenesis, and this finding may be useful for the development of novel pharmaceutical and cosmetic agents.

• BMB Reports
• /
• 제36권2호
• /
• pp.207-213
• /
• 2003

Peroxisome proliferator-activated receptors (PPARs) are orphan nuclear hormone receptors that are known to control the expression of genes that are involved in lipid homeostasis and energy balance. PPARs activate gene transcription in response to a variety of compounds, including hypolipidemic drugs. Most of these compounds have high affinity to the ligand-binding domain (LBD) of PPARs and cause a conformational change within PPARs. As a result, the receptor is converted to an activated mode that promotes the recruitment fo co-activators such as the steroid receptor co-activator-1 (SRC-1). Based on the activation mechanism of PPARs (the ligand binding to $PPAR{\gamma}$ induces interactions of the receptor with transcriptional co-activators), we performed Western blot and ELISA. These showed that the indomethacin, a $PPAR{\gamma}$ ligand, increased the binding between $PPAR{\gamma}$ and SRC-1 in a ligand dose-dependent manner. These results suggested that the in vitro conformational change of $PPAR{\gamma}$ by ligands was also induced, and increased the levels of the ligand-dependent interaction with SRC-1. Collectively, we developed a novel and useful ELISA system for the mass screening of $PPAR{\gamma}$ ligands. This screening system (based on the interaction between $PPAR{\gamma}$ and SRC-1) may be a promising system in the development of drugs for metabolic disorders.

• Genomics & Informatics
• /
• 제14권3호
• /
• pp.104-111
• /
• 2016

Zika virus (ZIKV) is a mosquito borne pathogen, belongs to Flaviviridae family having a positive-sense single-stranded RNA genome, currently known for causing large epidemics in Brazil. Its infection can cause microcephaly, a serious birth defect during pregnancy. The recent outbreak of ZIKV in February 2016 in Brazil realized it as a major health risk, demands an enhanced surveillance and a need to develop novel drugs against ZIKV. Amodiaquine, prochlorperazine, quinacrine, and berberine are few promising drugs approved by Food and Drug Administration against dengue virus which also belong to Flaviviridae family. In this study, we performed molecular docking analysis of these drugs against nonstructural 3 (NS3) protein of ZIKV. The protease activity of NS3 is necessary for viral replication and its prohibition could be considered as a strategy for treatment of ZIKV infection. Amongst these four drugs, berberine has shown highest binding affinity of -5.8 kcal/mol and it is binding around the active site region of the receptor. Based on the properties of berberine, more similar compounds were retrieved from ZINC database and a structure-based virtual screening was carried out by AutoDock Vina in PyRx 0.8. Best 10 novel drug-like compounds were identified and amongst them ZINC53047591 (2-(benzylsulfanyl)-3-cyclohexyl-3H-spiro[benzo[h]quinazoline-5,1'-cyclopentan]-4(6H)-one) was found to interact with NS3 protein with binding energy of -7.1 kcal/mol and formed H-bonds with Ser135 and Asn152 amino acid residues. Observations made in this study may extend an assuring platform for developing anti-viral competitive inhibitors against ZIKV infection.

• 대한화학회지
• /
• 제40권4호
• /
• pp.264-272
• /
• 1996

ASED-MO(Atom Superposition and Electoron Delocalization-Molecular Orbtal)이론을 이용하여 Pt(lll)과 ${\upsilon}-Al_2O_3$(III) 표면 모델에 대한 계면간 결합 세기에 관해 연구하였다. $Al^{3+}$의 환원 정도가는 알루미나 뭉치(cluster)에 대한 산소와 알루미늄의 비에 따라 달라진다. $Al^{3+}$의 환원 정도가 크면 클수록 Pt 원소들에 대해 강한 결합 에너지를 가진다. 산소로 덮인 ${\gamma}-Al_{20}_3$(III) 표면과 Pt 계면간 결합이 매우 약하지만 백금의 산화 조건에서의 결합은 매우 강하다. 백금 표면에서 부분적으로 빈 O-2p 띠(band)와 $Al^{3+}$ dangling surface orbital로 전하가 이동하는 전하이동(charge transfer) 메카니즘에 의해 백금과 알루미나 계면간 결합은 가능하다.

• 생명과학회지
• /
• 제15권6호
• /
• pp.935-940
• /
• 2005

Coumarine이 부착된 인산결합 단백질 (PBP-MDCC)의 형광변화가 뉴클레오사이드 삼인산 가수분해과정에서 배출된 무기 인산의 양을 측정하기 위해 관찰되었다. PBP-MDCC 정제후, 형광 방출 스펙트럼은 형광세기가 PBP-MDCC의 몰비을로 약 $70\%$까지 직선형태로 증가하는 것을 보였다. 형광 신호와 인산 기준물질과의 상호관계 측정이 인산 농도-형광세기 표준곡선을 구하기 위하여 stopped-flow 기구에서 행하여졌다. dTTP 가수분해로 부터 나오는 에너지를 이용하여 이중나선 DNA를 풀어주는 단백질인 T7박테리오파지 나선효소를 dPTT라 반응 시켰을 때, 형광변화를 배출된 인산의 양으로 전환할 수 있었다. 인산 배출 결과는 단일가닥 Ml3 DNA가 T7나선 효소에 의한 dTTP가수분해반응을 여러배 증가시키는 것을 보인다. 뉴클레오타이드 삼인산 가수분해 반응에 있어서 종말점 분석 대신에, PBP-MDCC에 의한 연속적인 인산 배출 분석이 배출된 인산을 측정하는데 있어서 쉽고 편리한 방법임을 보였다.

• 한국구조물진단유지관리공학회 논문집
• /
• 제26권5호
• /
• pp.119-126
• /
• 2022

본 연구는 내진설계가 되어 있지 않은 필로티 건축물의 부족한 횡력을 보강할 수 있는 외부부착형 내진보강공법(Binding Column Method, BCM)을 제안하였다. 또한, 제안된 내진보강공법을 대상으로 보강실험체 4개, 기준 실험체 1개를 제작하여 반복가력 실험을 통하여 보강 전·후의 내진성능향상 효과를 검토하였다. 실험 결과, 기준 실험체(SC1)는 급격한 강도저하와 함께 취성적인 전단파괴의 양상을 나타낸 반면, BCM 공법을 적용한 실험체(SC2, SC3, SC4, SC5)는 강도 및 강성의 증가와 함께 에너지 흡수 능력이 큰 타원형의 이력특성을 나타내었다. 또한, 간격이 좁고 토크가 크며, L자형 강판의 두께가 두꺼울수록 보강효과가 향상됨을 알 수 있다. BCM공법 중 전단보강간격이 작고, 조임력 값이 크며, 연결철물이 두꺼운 SC4실험체가 가장 뛰어난 내진성능보강 효과를 나타내었다.

• Natural Product Sciences
• /
• 제28권2호
• /
• pp.45-52
• /
• 2022

The identification of Plasmodium falciparum enoyl acyl-carrier protein reductase (pfENR) is considered as a potential biological target against malaria. Trema orientalis is considered a rich source of phytochemicals useful in malaria treatment. This study evaluated the in-vitro inhibitory activity of the extract and isolated compounds of T. orientalis leaf; the isolated compounds and the analogues of the most active compound were subjected to in-silico molecular docking studies on pfENR. The methanolic extract of T. orientalis was subjected to repeated chromatographic separation which led to the isolation of some compounds. The isolated compounds from the plant were examined for their antimalarial activity using β-hematin inhibition assay. Virtual screening via molecular docking and ADMET studies were conducted to gain insight into the mechanism of binding of ligand and to identify effective pfENR inhibitors. The isolated compounds and the analogues of the most active isolates were gotten from PubChem library for use in docking study. Hexacosanol and β-sitosterol showed inhibition of the β-hematin formation. The docking results showed that hexacosanol, β-sitosterol and the analogues of β-sitosterol displayed binding energy ranging between -6.1 kcal/mol and -11.6 kcal/mol. Sitosterol glucoside has the highest docking score. Some of the ligands showed more binding affinity than known bioactive compounds used as reference. Analogues of β-sitosterol has been shown to be potential inhibitors of pfENR, therefore, the findings from this study suggest that sitosterol glucoside and ergosterol peroxide could act as antimalarial agents after further lead optimisation investigations.

• Coupled systems mechanics
• /
• 제2권2호
• /
• pp.147-157
• /
• 2013

We numerically investigate the electronic band structure of carbon nanotubes (CNTs) under radial corrugation. Hydrostatic pressure application to CNTs leads to a circumferential wave-like deformation of their initially circular cross-sections, called radial corrugations. Tight-binding calculation was performed to determine the band gap energy as a function of the amplitude of the radial corrugation. We found that the band gap increased with increasing radial corrugation amplitude; then, the gap started to decline at a critical amplitude and finally vanished. This non-monotonic gap variation indicated the metal-semiconductor-metal transition of CNTs with increasing corrugation amplitude. Our results provide a better insight into the structure-property relation of CNTs, thus advancing the CNT-based device development.

• Transactions on Electrical and Electronic Materials
• /
• 제15권6호
• /
• pp.305-308
• /
• 2014

Organosilyl-modified and star-shaped poly (${\varepsilon}$-caprolactone) (m-PCL) was prepared, and added to polymethylsilsesquioxane (PMSSQ), to make composites. The end groups of m-PCL are chemically similar to PMSSQ, and m-PCL mixed well with PMSSQ in the composite. Porous PMSSQ film was made by further calcination of the composite film at elevated temperature. m-PCL-templated PMSSQ and the as-prepared porous PMSSQ were structurally, optically, and thermally characterized in thin films. The chemical binding of m-PCL and PMSSQ effectively suppressed the phase separation of PMSSQ and m-PCL during the curing process. After calcination at elevated temperature, there remained many pores in the PMSSQ matrix. The refractive indices of the resulting porous PMSSQ thin films decreased with increase of the film porosities, depending on the initial m-PCL loadings.