• Journal of Oriental Neuropsychiatry
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• v.15 no.1
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• pp.77-86
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• 2004

Objective : This study was performed to investigate the agonistic activity of Chunmajeongal-tang extract to the $GABA_A/benzodiazepine$ receptor complex. Methods : Male mice and Sprague-Dawley rats were used for this experiment. Chunmajeongal-tang Prescription was extracted with 80% methanol, evaporated in vacuo and dried with freeze dryer. The agonistic activity to the GABA/ benzodiazepine receptor complex and GABA transaminase activity were measured in vitro. Results : Chunmajeongal-tang extract inhibited dose-dependently the binding of [3H]Ro15-1788, an antagonist on GABA/benzodiazepine receptor complex, in rat cerebral cortices, showing $82.4{\pm}4.12%$ inhibition at a dose of 5.0 mg/kg. This extract inhibited dose-dependently the binding of [3H]flunitrazepam, an agonist on GABA/benzodiazepine receptor complex, in rat cerebral cortices, showing $5.6{\pm}1.24%$ inhibition. Furthermore, Chunmajeongal-tang extract inhibited the binding of [3H]flunitrazepam in the presence of GABA/NaCI with $13.2{\pm}0.44%$ inhibition, its inhibitory effect exhibited a positive GABA shift, which means that this extract activates a GABAergic neurotransmission.

• YAKHAK HOEJI
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• v.60 no.2
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• pp.78-84
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• 2016

N-Phenylthiourea derivatives and catechol oxidase receptor complex was studied using molecular mechanics method. The starting structure was adopted from the protein databank and the calculation of energy minimization and molecular dynamics was performed with AMBER package. The molecular dynamics showed that the simulation time span of 20 ns was long enough to observe the interaction profile and stationary ligand-receptor configuration in the complex. The conformation of the ligand was related to the interaction to the receptor and the efficacy was also interpreted in this context.

• Interdisciplinary Bio Central
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• v.4 no.4
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• pp.13.1-13.6
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• 2012

The advanced glycation endproducts receptor (AGER) is a multiligand signal transduction receptor. One of its ligands, S100b molecules activates vascular smooth muscle cells and endothelial cells via its receptor, thus triggering activation of signaling cascades and generation of cytokines and proinflammatory molecules. Ubiquitin-conjugating enzyme Ubc9 is an E2 conjugating enzyme that transfers the activated small ubiquitin-related modifier to protein substrates, and thus it plays a critical role in SUR-Mylation-mediated cellular pathways. Previous studies have shown that both AGE-R and Ubc9 play roles in diverse cellular signaling pathways. However, until recently, little attention has been paid to interactions between AGE-R and Ubc9. In this study, sequence database searches allowed us to identify a potential interaction motif between AGE-R and Ubc9. The subsequent biochemical and molecular biological analysis suggested that there may be specificity in AGE-R and Ubc9 complex signaling in atherosclerosis and cancer cells in a cell-type specific manner. Although the determinant for specificity in AGE-R and Ubc9 complex signaling in cancer cells and atherosclerosis is yet to be determined, this study provides the basis to develop a specific therapeutic application of AGE-R, SURM (small ubiquitin-related modifier)-1, and Ubc9 complex activation pathways in atherosclerosis, diabetes, cancer and inflammatory diseases.

• Journal of Integrative Natural Science
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• v.10 no.1
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• pp.14-19
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• 2017

Neuromedin, a neuropeptide, which is involved in various functions that include contractile activity on smooth muscle, controlling the blood flow and ion transport in the intestine, increased blood pressure and regulation of adrenocortical function. It is involved in the pathophysiology of various immune mediated inflammatory diseases like asthma. In this study, we have performed protein-protein docking analysis of neuromedin U - neuromedin U receptor 1 complex. We have developed homology models of neuromedin U, and selected a reliable model using model validation. The model was docked with the receptor model, to analyse the crucial interactions of the complex. This study could be helpful as a tool in developing novel and potent drugs for the diseases related with neuromedin U receptor 1.

• Molecules and Cells
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• v.27 no.2
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• pp.183-190
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• 2009

The plasma membrane-localized BRASSINOSTEROID-INSENSITIVE1 (BRI1) and BRI1-ASSOCIATED KINASE1 (BAK1) are a well-known receptor pair involved in brassinosteroids (BR) signaling in Arabidposis. The formation of a receptor complex in response to BRs and the subsequent activation of cytoplasmic domain kinase activity share mechanistic characteristics with animal receptor kinases. Here, we demonstrate that BRI1 and BAK1 are BR-dependently phosphorylated, and that phosphorylated forms of the two proteins persist for different lengths of time. Mutations of either protein abolished phosphorylation of the counterpart protein, implying transphosphorylation of the receptor kinases. To investigate the specific amino acids critical for formation of the receptor complex and activation of BAK1 kinase activity, we expressed several versions of BAK1 in yeast and plants. L32E and L46E substitutions resulted in a loss of binding of BAK1 to BRI1, and threonine T455 was essential for the kinase activity of BAK1 in yeast. Transgenic bri1 mutant plants overexpressing BAK1(L46E) displayed reduced apical dominance and seed development. In addition, transgenic wild type plants overexpressing BAK1(T455A) lost the phosphorylation activity normally exhibited in response to BL, leading to semi-dwarfism. These results suggest that BAK1 is a critical component regulating the duration of BR efficacy, even though it cannot directly bind BRs in plants.

• Journal of Integrative Natural Science
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• v.11 no.2
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• pp.101-106
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• 2018

Corticotropin - releasing hormone receptor 1 (CRHR1) forms an integral part of the pathophysiology of disorders like post-traumatic stress disorder, stress, anxiety, addiction, and depression. Hence it is essential to look for new, potent and structure-specific inhibitors of CRHR1. We have analysed the protein-protein interaction complexes of the CRHR1 receptor with its native ligand CRF and full agonist Sauvagine. The structure of Sauvagine was predicted using homology modelling. We have identified that the residues TYR253, ASP254, GLU256, GLY265, ARG1014 and LY1060 are important in the formation of protein-protein complex formation. Future studies on these residues could throw light on the crucial structural features required for the formation of CRHR1-inhibitor complex and in studies that try to solve the structural complexities of CRHR1.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.9
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• pp.1261-1267
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• 2003

We have investigated whether HspBP1, a Hsp70 binding protein, could have effect on the assembly of the bovine progesterone receptor (bPR) with a chaperone complex consisting of bovine Hsp90 (bHsp90), bovine Hsp70 (bHsp70), Hop, Ydj-1, and p23. The bPR, isolated in its native conformation, loses its function to interact with progesterone hormone in the absence of this protein complex. However, in the presence of bHsp90, bHsp70, Hop, p23 and Ydj-1, its function could be restored in vitro. Our findings here indicate that the inclusion of HspBP1 to five-protein system prevented the proper assembly of progesterone receptor-chaperone complex and induce the loss of bPR ability to interact with hormone. Immunoprecipitation assays of bPR with HspBP1 show that the presence of HspBP1 did not have any effect on the assembly of Ydj-1 and bHsp70 with the progesterone receptor. However, further assembly of Hsp90, Hop and p23 was completely prevented and the function of the bPR was lost. In vitro competition and protein folding assays indicated that the binding of HspBP1 to bHsp70 prevented the ternary complex formation of bHsp70, bHsp90, and Hop. These results indicate that HspBP1 is a negative regulator of the assembly of Hsp90, Hop and Hsp70, and thus, prevent the proper maturation of unliganded bPR with chaperones assembly system.

• Biomedical Science Letters
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• v.9 no.2
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• pp.67-74
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• 2003

Viral and non-viral vectors have been used in the delivery of genetic materials into animal cells and tissues, with each approach having pros and cons. Non-viral vectors have many useful merits such as easy preparation, low immunity and size tolerance of a transgene when compared to those of viral vectors. Delivery specificity may be achieved by complex formation between receptor ligands and a non-viral vector. In the present study, non-viral vector systems are investigated in an effort to find a practical delivery means for gene therapy, Receptor-ligand interaction between transferrin-receptor and transferrin was utilized for efficient gene transfer into cancer cells. A plasmid vector, pcDNA3 (LacZ) was ligated with a small duplexed oligo fragment in which a Biotin- VN$^{TM}$ phosphoramidite was placed in the middle of the oligo. The plasmid vector labeled by biotin was then conjugated with biotin-labeled transferrin via streptavidin. This trimeric conjugates were delivered to a hepatoma cell line, HepG2. The delivery efficiency of the trimeric conjugate was 2-fold higher than that of cationic liposomes used for transfection of a plasmid vector. These results demonstrate that a plasmid vector can be efficiently transferred into cells by forming a trimeric complex of plasmid vector-linker-ligand.

• BMB Reports
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• v.32 no.5
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• pp.419-428
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• 1999

Tumor necrosis factor (TNF) receptor members have unique structures composed of 2-4 cysteine - rich pseudorepeats in the extracellular domain. On ligation by trimeric ligand molecules, oligomerization of three receptor molecules occurs, which in turn activates the receptor and recruits intracellular signaling molecules to the cytoplasmic tail to initiate biological events. Recently, the numbers of tumor necrosis factor receptor and ligand family members have been rapidly expanding. Functional characterization of the new members has indicated redundant roles with other known members as well as provided insights into novel functions. In particular, identification of soluble decoy receptors which have the ability to bind multiple ligands highlights a complex control mechanism of immune responses by these molecules. Studies of the new members have also revealed that the TNF receptor and ligand family members play an important role in other than the immune system.

• Journal of Microbiology and Biotechnology
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• v.25 no.2
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• pp.247-254
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• 2015

In this presentation, I describe the expression and purification of the recombinant liver X receptor β-ligand binding domain proteins in E. coli using a commercially available double cistronic vector, pACYCDuet-1, to express the receptor heterodimer in a single cell as the soluble form. I describe here the expression and characterization of a biologically active heterodimer composed of the liver X receptor β-ligand binding domain and retinoid X receptor α-ligand binding domain. Although many of these proteins were previously seen to be produced in E. coli as insoluble aggregates or "inclusion bodies", I show here that as a form of heterodimer they can be made in soluble forms that are biologically active. This suggests that co-expression of the liver X receptor β-ligand binding domain with its binding partner improves the solubility of the complex and probably assists in their correct folding, thereby functioning as a type of molecular chaperone.