• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.191-198
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• 2016

The vitamin D receptor (VDR) is a member of the nuclear receptor (NR) superfamily. The VDR binds to active vitamin $D_3$ metabolites, which stimulates downstream transduction signaling involved in various physiological activities such as calcium homeostasis, bone mineralization, and cell differentiation. Quercetin is a widely distributed flavonoid in nature that is known to enhance transactivation of VDR target genes. However, the detailed molecular mechanism underlying VDR activation by quercetin is not well understood. We first demonstrated the interaction between quercetin and the VDR at the molecular level by using fluorescence quenching and saturation transfer difference (STD) NMR experiments. The dissociation constant ($K_d$) of quercetin and the VDR was $21.15{\pm}4.31{\mu}M$, and the mapping of quercetin subsites for VDR binding was performed using STD-NMR. The binding mode of quercetin was investigated by a docking study combined with molecular dynamics (MD) simulation. Quercetin might serve as a scaffold for the development of VDR modulators with selective biological activities.

• BMB Reports
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• v.48 no.7
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• pp.367-368
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• 2015

It has long been thought that glucocorticoid receptor (GR) functions as a DNA-binding transcription factor in response to its ligand (a glucocorticoid) and thus regulates various cellular and physiological processes. It is also known that GR can bind not only to DNA but also to mRNA; this observation points to the possible role of GR in mRNA metabolism. Recent data revealed a molecular mechanism by which binding of GR to target mRNA elicits rapid mRNA degradation. GR binds to specific RNA sequences regardless of the presence of a ligand. In the presence of a ligand, however, the mRNA-associated GR can recruit PNRC2 and UPF1, both of which are specific factors involved in nonsense-mediated mRNA decay (NMD). PNRC2 then recruits the decapping complex, consequently promoting mRNA degradation. This mode of mRNA decay is termed "GR-mediated mRNA decay" (GMD). Further research demonstrated that GMD plays a critical role in chemotaxis of immune cells by targeting CCL2 mRNA. All these observations provide molecular insights into a previously unappreciated function of GR in posttranscriptional regulation of gene expression. [BMB Reports 2015; 48(7): 367-368]

• Bulletin of the Korean Chemical Society
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• v.35 no.10
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• pp.3015-3020
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• 2014

The behavior of benzo[a]pyrene-7,8-dione (BPQ) in aqueous solution and its interaction with native DNA was investigated using conventional absorption and linear dichroism (LD) spectroscopy. The appearance of a broad absorption maximum at long wavelengths and its proportional relationship to solvent polarizability suggested that BPQ adopts a aggregated state for all solutions examined. Disappearance of this absorption band at higher temperatures in aqueous solution also supported BPQ aggregation. When associated with DNA absorption spectral properties were essentially the same as that in aqueous solution. However, two isosbestic wavelengths were found in the concentration-dependent absorption spectrum of the BPQ-DNA complex, suggesting the presence of at least two or more DNA-bound BPQ species. Both species produced $LD^r$ spectra whose magnitude in BPQ absorption region is larger or comparable to that in the DNA absorption region, suggesting that the molecular BPQ plane is near perpendicular relative to the local DNA helical axis. Therefore, BPQ molecules are aligned along the DNA stem in both DNA-aggregated BPQ species.

• Bulletin of the Korean Chemical Society
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• v.34 no.10
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• pp.2895-2899
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• 2013

Direction of intercalation to DNA of the planar dipyrido[3,2-a:2',3'-c]phenazine ligands (dppz) of a bis-Ru(II) complex namely, $[Ru(1,10-phenanthroline)_2dipyrido[3,2-a:2^{\prime},3^{\prime}-c]phenazine]^{2+}$ linkered by a 1,3-bis(4-pyridyl)propane, was investigated by probing the behavior of 4',6-diamidino-2-phenylindole (DAPI) that bound deep in the minor groove. Bis-intercalation of DPPZ resulted in a little blue shift and hyperchromism in DAPI absorption band, and a large decrease in DAPI fluorescence intensity which accompined by an increase in the dppz emission intensity. Diminishing the intenisty of the positive induced circular dichroism (CD) and linear dichroism (LD) were also observed. These spectral changes indicated that insertion of dppz ligand caused the change of the binding mode of DAPI, which probably moved to the exterior of DNA from the minor groove and interacted with the phospghate groups of DNA by electrostatic interaction. At the surface of DNA, DAPI binds at the phosphate groups of DNA by electrostatic attraction. Consequently, this observation indicated that the dppz ligand intercalated from the minor groove.

• Bulletin of the Korean Chemical Society
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• v.34 no.4
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• pp.1212-1220
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• 2013

The human coagulation factor XI (FXI) is a serine protease that plays a significant role in blocking of the blood coagulation cascade as an attractive antithrombotic target. Selective inhibition of FXIa (an activated form of factor XI) disrupts the intrinsic coagulation pathway without affecting the extrinsic pathway or other coagulation factors such as FXa, FIIa, FVIIa. Furthermore, targeting the FXIa might significantly reduce the bleeding side effects and improve the safety index. This paper reports on a docking-based three dimensional quantitative structure activity relationship (3D-QSAR) study of the potent FXIa inhibitors, the chloro-phenyl tetrazole scaffold series, using comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) methods. Due to the characterization of FXIa binding site, we classified the alignment of the known FXIa inhibitors into two groups according to the docked pose: S1-S2-S4 and S1-S1'-S2'. Consequently, highly predictive 3D-QSAR models of our result will provide insight for designing new potent FXIa inhibitors.

• Proceedings of the Korea Crystallographic Association Conference
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• 2003.05a
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• pp.17-17
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• 2003

tRNA (m¹ G37) methyltransferase (TrmD) catalyze s the trans for of a methyl group from S-adenosyl-L-methionine (AdoMet) to G/sup 37/ within a subset of bacterial tRNA species, which have a residue G at 36th position. The modified guanosine is adjacent to and 3' of the anticodon and is essential for the maintenance of the correct reading frame during translation. We have determined the first crystal structure of TrmD from Haemophilus influenzae, as a binary complex with either AdoMet or S-adenosyl-L-homocysteine (AdoHcy), as a ternary complex with AdoHcy/phosphate, and as an apo form. The structure indicates that TrmD functions as a dimer (Figure 1). It also suggests the binding mode of G/sup 36/G/sup 37/ in the active site of TrmD and catalytic mechanism. The N-terminal domain has a trefoil knot, in which AdoMet or AdoHcy is bound in a novel, bent conformation. The C-terminal domain shows a structural similarity to DNA binding domain of trp or tot repressor. We propose a plausible model for the TrmD₂-tRNA₂ complex, which provides insights into recognition of the general tRNA structure by TrmD (Figure 2).

• Journal of Integrative Natural Science
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• v.7 no.4
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• pp.241-252
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• 2014

A series of N-benzoylated ligands incorporating three different benzoyl groups 2,2'-(benzoyliminodiethylene)-4-substituted phenols ($L^{1,4,7}$), 2,2'-(4-nitrobenzoyliminodiethylene)-4-substituted phenols ($L^{2,5,8}$) and 2,2'-(3,5-dinitrobenzoyliminodiethylene)-4-substituted phenols ($L^{3,6,9}$) were synthesized and characterized by IR, $^1H$ NMR, $^{13}C$ NMR and mass spectroscopy. The In vitro antibacterial activity of investigated ligands were tested against human pathogenic bacteria such as four Gram (-) Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus, Vibrio cholera, Vibrio harveyi and two Gram (+) Staphylococcus aureus, Streptococcus mutans. Furthermore, docking studies were undertaken to gain insight into the possible binding mode of these compounds with the binding site of the topoisomerase II (PDB: 4FM9) enzyme which is involved in DNA superhelicity and chromosome seggregation. The N-benzoylated derivatives $L^{5,7,8}$ have significant anticancer activity as Topoisomerase inhibitors. The ligands $L^5$ and $L^8$ were tested for their anticancer activity against human liver adenocarcinoma (HepG2) cell line with the MTT assay.

• JSTS:Journal of Semiconductor Technology and Science
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• v.7 no.3
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• pp.151-160
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• 2007

We report the label-free biomolecules detection based on nanomechanical micro cantilevers operated in dynamic mode for detection of two marker proteins (myoglobin and creatin kinase-MB (CK-MB)) of acute myocardical infarctions. When the specific binding between the antigen and its antibody occurred on the fuctionalized microcantilever surface, mechanical response (i.e. resonant frequency) of microcantilevers was changed in lower frequency range. We performed the label-free biomolecules detection of myoglobin and CK-MB antigen in the low concentration (clinical threshold concentration range) as much as 1 ng/ml from measuring the dynamic response change of micro cantilevers caused by the intermolecular force. Moreover, we estimate the surface stress on the dynamic microcantilevers generated by specific antibody-antigen binding. It is suggested that our dynamic microcantilevers may enable one to use the sensitive label-free biomolecules detection for application to the disease diagnosis system based on mechanical immuno-sensor.

• Bulletin of the Korean Chemical Society
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• v.34 no.8
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• pp.2466-2472
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• 2013

Human immunodeficiency virus type-1 (HIV-1) is a causative agent of Acquired immunodeficiency syndrome (AIDS), which has affected a large population of the world. Viral envelope glycoprotein (gp120) is an intrinsic protein for HIV-1 to enter into human host cells. Molecular docking guided molecular dynamics (MD) simulation was performed to explore the interaction mechanism of heterobiaryl derivative with gp120. MD simulation result of inhibitor-gp120 complex demonstrated stability. Our MD simulation results are consistent with most of the previous mutational and modeling studies. Inhibitor has an interaction with the CD4 binding region. Van der Waals interaction between inhibitor and Val255, Thr257, Asn425, Met426 and Trp427 were important. This preliminary MD model could be useful in exploiting heterobiaryl-gp120 interaction in greater detail, and will likely to shed lights for further utilization in the development of more potent inhibitors.

• Archives of Pharmacal Research
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• v.29 no.11
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• pp.1006-1017
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• 2006

A series of 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-one, 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-thione and 2, 2'-dithiobis 3-(substituted-benylidene)-1, 3-dihydro-indole derivatives was investigated as inhibitor of $p60^{c-Src}$tyrosine kinase by performing receptor docking studies and inhibitory activity toward tyrosine phosphorylation. Some compounds were shown to be docked at the site, where the selective inhibitor PP1 [1-tert-Butyl-3-p-tolyl-1H-pyrazolo[3,4-d]pyrimidine-4-yl-amine] was embedded at the enzyme active site. Evaluation of all compounds for the interactions with the parameters of lowest binding energy levels, capability of hydrogen bond formations and superimposibility on enzyme active site by docking studies, it can be assumed that 3-(substituted-benzylidene)-1, 3-dihydro-indolin-2-one and thione derivatives have better interaction with enzyme active site then 2, 2'-dithiobis 3-(substituted-benzylidene)-1, 3-dihydro indole derivatives. The test results for the inhibitory activity against tyrosine kinase by Elisa method revealed that 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-thione derivatives have more activity then 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-one derivatives.