• BMB Reports
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• v.52 no.2
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• pp.119-126
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• 2019

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) initiates the extrinsic apoptotic pathway through formation of the death-inducing signaling complex (DISC), followed by activation of effector caspases. TRAIL receptors are composed of death receptors (DR4 and DR5), decoy receptors (DcR1 and DcR2), and osteoprotegerin. Among them, only DRs activate apoptotic signaling by TRAIL. Since the levels of DR expressions are higher in cancer cells than in normal cells, TRAIL selectively activates apoptotic signaling pathway in cancer cells. However, multiple mechanisms, including down-regulation of DR expression and pro-apoptotic proteins, and up-regulation of anti-apoptotic proteins, make cancer cells TRAIL-resistant. Therefore, many researchers have investigated strategies to overcome TRAIL resistance. In this review, we focus on protein regulation in relation to extrinsic apoptotic signaling pathways via ubiquitination. The ubiquitin proteasome system (UPS) is an important process in control of protein degradation and stabilization, and regulates proliferation and apoptosis in cancer cells. The level of ubiquitination of proteins is determined by the balance of E3 ubiquitin ligases and deubiquitinases (DUBs), which determine protein stability. Regulation of the UPS may be an attractive target for enhancement of TRAIL-induced apoptosis. Our review provides insight to increasing sensitivity to TRAIL-mediated apoptosis through control of post-translational protein expression.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2004.11a
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• pp.221-233
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• 2004

Molecular docking falls into the general category of global optimization problems since its main purpose is to find the most stable complex consisting of a receptor and its ligand. Conformational space annealing (CSA), a powerful global optimization method, is incorporated with the Tinker molecular modeling package to perform molecular docking simulations of six receptor-ligand complexes (3PTB, 1ULB, 2CPP, 1STP, 3CPA and 1PPH) from the Protein Data Bank. In parallel, Monte Carlo with minimization (MCM) method is also incorporated into the Tinker package for comparison. The energy function, consisting of electrostatic interactions, van der Waals interactions and torsional energy terms, is calculated using the AMBER94 all-atom empirical force field. Rigid docking simulations for all six complexes and flexible docking simulations for three complexes (1STP, 3CPA and 1PPH) are carried out using the CSA and the MCM methods. The simulation results show that the docking procedures using the CSA method generally find the most stable complexes as well as the native -like complexes more efficiently and accurately than those using the MCM, demonstrating that CSA is a promising search method for molecular docking problems.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.527-538
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• 2019

Background: Ginsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor (ER) via mitogen-activated protein kinase-mediated pathway. Our study aimed to delineate the mechanisms by which Rg1 activates the rapid ER signaling pathways. Methods: ER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidney HEK293 cells were treated with Rg1 ($10^{-12}M$, $10^{-8}M$), $17{\beta}$-estradiol ($10^{-8}M$), or vehicle. Immunoprecipitation was conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or their inhibitors were applied. Results: Rg1 rapidly induced $ER{\alpha}$ translocation to plasma membrane via caveolin-1 and the formation of signaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator of nongenomic activity of ER (MNAR), $ER{\alpha}$, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase (MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interfering RNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in these cells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor (EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). The increase in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could be abolished by G15. Conclusion: Ginsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.

• BMB Reports
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• v.51 no.1
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• pp.21-26
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• 2018

Delta-like ligand 4 (DLL4) expression in endothelial cells is intimately associated with angiogenic sprouting and vascular remodeling, but the precise mechanism of transcriptional regulation of DLL4 remains incompletely understood. Here, we showed that LIM-domain binding protein 2 (LDB2) plays an important role in regulating basal DLL4 and VEGF-induced DLL4 expression. Knockdown of LDB2 using siRNA enhanced endothelial sprouting and tubular network formation in vitro. Injection of ldb2-morpholino resulted in defective development of intersegmental vessels in zebrafish. Reduction or over-expression of LDB2 in endothelial cells decreased or increased DLL4 expression. LDB2 regulated DLL4 promoter activity by binding to its promoter region and the same promoter region was occupied and regulated by the LMO2/TAL1/GATA2 complex. Interestingly, LDB2 also mediated VEGF-induced DLL4 expression in endothelial cells. The regulation of DLL4 by the LDB2 complex provides a novel mechanism of DLL4 transcriptional control that may be exploited to develop therapeutics for aberrant vascular remodeling.

• Macromolecular Research
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• v.14 no.2
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• pp.166-172
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• 2006

This is a short review article of our recent studies on the ATP-induced, allosteric conformational transition of the chaperonin GroEL complex by solution X-ray scattering. We used synchrotron X-ray scattering with a two-dimensional, charge-coupled, device-based X-ray detector to study (1) the specificity of the chaperonin GroEL for its ligand that induced the allosteric transition, and (2) the identification of the allosteric transition of GroEL in its complicated kinetics induced by ATP. Due to the dramatically increased sensitivity of the X-ray scattering technique based on the use of the two dimensional X-ray detector and synchrotron radiation, different allosteric conformational states of GroEL populated under different conditions were clearly distinguished from each other. It was concluded that solution X-ray scattering is an extremely powerful tool for investigating the equilibrium and kinetics of cooperative conformational transitions of oligomeric protein complex, especially when combined with other spectroscopic techniques such as fluorescence spectroscopy.

• Development and Reproduction
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• v.22 no.4
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• pp.351-360
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• 2018

The adipogenesis is a maturation process of pre-adipocyte cell into mature lipid-filled adipocyte cell. The adipogenesis begins at the late prenatal stage and continues until the early postnatal age. Because the adipogenesis and formation of adipose tissue persist during postnatal period and are precisely regulated by the action of numerous gene products, the present research was attempted to determine the expressional patterns of adipose tissue-associated genes in the rat epididymal fat pad at different postnatal ages, from 7 days to 2 years of ages, using a quantitative real-time PCR analysis. The basal expression levels of CCAAT/enhancer binding protein gamma, sterol regulatory element binding transcription factor 1, fatty acid binding protein 4, adiponectin, leptin, and resistin at the early postnatal ages were significantly lower than those at the elderly ages, even though a fluctuation of expressional levels was observed at some ages. The lowest expressional level of delta like non-canonical Notch ligand 1 was detected at 44 days and 5 months of ages. The expression of peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) was the highest at 44 days of age, followed by a diminished expression of $PPAR{\gamma}$ at the elderly ages. These results indicate the existence of a complex regulatory mechanism(s) for expression of adipose tissueassociated genes in the rat epididymal fat during postnatal period.

• Biodesign
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• v.6 no.4
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• pp.100-102
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• 2018

Autophagy is a degradation pathway that targets many cellular components and plays a particularly important role in protein degradation and recycling. This process is very complex and several proteins participate in this process. One of them, P62/SQSTM1, is related to the N-end rule and induces protein degradation through autophagy. The P62/SQSTM1 makes a huge oligomer, and this oligomerization is known to play an important role in its mechanism. This oligomerization takes two steps. First, the PB1 domain of P62/SQSTM1 makes the base oligomer, and then, when the ligand binds to the ZZ domain of P62/SQSTM1, it induces a higher oligomer by the disulfide bond of the two cysteines. To understand the oligomerization mechanism of P62/SQSTM1, we need to know the dimerization of the PB1 domain. In this study, crystals of PB1 dimer were made and the crystals were diffracted by X-ray to collect usable data up to 3.2A. We are analyzing the structure using the molecular replacement (MR) method.

• Genomics & Informatics
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• v.21 no.2
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• pp.17.1-17.12
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• 2023

Coronavirus has left severe health impacts on the human population, globally. Still a significant number of cases are reported daily as no specific medications are available for its effective treatment. The presence of the CD147 receptor (human basigin) on the host cell facilitates the severe acute respiratory disease coronavirus 2 (SARS-CoV-2) infection. Therefore, the drugs that efficiently alter the formation of CD147 and spike protein complex could be the right drug candidate to inhibit the replication of SARS-CoV-2. Hence, an e-Pharmacophore model was developed based on the receptor-ligand cavity of CD147 protein which was further mapped against pre-existing drugs of coronavirus disease treatment. A total of seven drugs were found to be suited as pharmacophores out of 11 drugs screened which was further docked with CD147 protein using CDOCKER of Biovia discovery studio. The active site sphere of the prepared protein was 101.44, 87.84, and 97.17 along with the radius being 15.33 and the root-mean-square deviation value obtained was 0.73 Å. The protein minimization energy was calculated to be -30,328.81547 kcal/mol. The docking results showed ritonavir as the best fit as it demonstrated a higher CDOCKER energy (-57.30) with correspond to CDOCKER interaction energy (-53.38). However, authors further suggest in vitro studies to understand the potential activity of the ritonavir.

• The Korean Journal of Mycology
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• v.17 no.3
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• pp.105-113
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• 1989

For selective purification of proteins in Pleurotus cornucopiae, affinity chromatography was performed by p-aminoanilinylsuccinyl-AH-Sepharose 4B gel synthesized by treating p-phenylene diamine with succinyl-AH-Sepharose 4B, which was prepared by treating AH-Sepharose 4B with succinic anhydride. The capacity of p-aminoanilinyl ligand group was 6.1 micromole per milliliter of gel. Total apparent molecular weight of the affinity proteins eluted from the synthesized gel was 167 KD, which were a protein complex of 130 KD and 37 KD. The contents of the nonpolar, polar, positively and/or negatively charged amino acids in the affinity protein were 44.57%, 24.75%, 21.25%, and 9.43%, respectively. Total apparent molecular weight of the affinity proteins eluted from the AH-Sepharose 4B gel was 95.2 KD, which were a protein complex of 61 KD, 31 KD and 3.2 KD. The contents of the nonpolar, positively and/or negatively charged amino acids in the affinity protein by AH-Sepharose 4B gel were 44.05%, 29.13%, and 12.91% respectively.

• Proceedings of the Korean Vacuum Society Conference
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• 2013.08a
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• pp.91-91
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• 2013

Imagine a world where we could biomanufacture hybrid nanomaterials having atomic-scale resolution over functionality and architecture. Toward this vision, a fundamental challenge in materials science is how to design and synthesize protein-like material that can be fully self-assembled and exhibit information-specific process. In an ongoing effort to extend the fundamental understanding of protein structure to non-natural systems, we have designed a class of short peptides to fold like proteins and assemble into defined nanostructures. In this talk, I will talk about new strategies to drive the self-assembled structures designing sequence of peptide. I will also discuss about the specific interaction between proteins and inorganics that can be used for the development of new hybrid solar energy devices. Splitting water into hydrogen and oxygen is one of the promising pathways for solar to energy convertsion and storage system. The oxygen evolution reaction (OER) has been regarded as a major bottleneck in the overall water splitting process due to the slow transfer rate of four electrons and the high activation energy barrier for O-O bond formation. In nature, there is a water oxidation complex (WOC) in photosystem II (PSII) comprised of the earthabundant elements Mn and Ca. The WOC in photosystem II, in the form of a cubical CaMn4O5 cluster, efficiently catalyzes water oxidation under neutral conditions with extremely low overpotential (~160 mV) and a high TOF number. The cluster is stabilized by a surrounding redox-active peptide ligand, and undergo successive changes in oxidation state by PCET (proton-coupled electron transfer) reaction with the peptide ligand. It is fundamental challenge to achieve a level of structural complexity and functionality that rivals that seen in the cubane Mn4CaO5 cluster and surrounding peptide in nature. In this presentation, I will present a new strategy to mimic the natural photosystem. The approach is based on the atomically defined assembly based on the short redox-active peptide sequences. Additionally, I will show a newly identified manganese based compound that is very close to manganese clusters in photosystem II.