• Journal of Applied Biological Chemistry
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• v.54 no.1
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• pp.56-62
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• 2011

Molecular docking of polyhydroxy substituted flavone analogues (1-25) as substrate molecules to the active site of tyrosinase (PDB ID: Deoxy-form (2ZMX) & Oxy-form (1WX2)) and Free-Wilson analysis were studied to understand the roles of hydroxyl substituents ($R_1-R_9$) in substrate molecules for the tyrosinase inhibitory activation. It is founded from Free-Wilson analysis that the $R_1$=hydroxyl among $R_1-R_9$ substituents had the strongest influence on the tyrosinase inhibitory activity. H-bonds between the hydroxyl substituents of substrate molecules and amino acid residues in the active site of tyrosinase were contributed to make a stable substrate-receptor complex compound. Particularly, it is proposed from the findings that the noncompetitive inhibitory activation would take place via H-bonding between peroxide oxygen (Per404) atom in the active site of tyrosinase and the hydroxyl substituents in substrate molecule.

• The Korean Journal of Zoology
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• v.23 no.3
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• pp.137-148
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• 1980

The effects of divalent cations, $Hg^{2+}, Cu^{2+}, Pb^{2+}, Cd^{2+}$, and $Mn^{2+}$ on the total ATPase activity of the fragmented sarcoplasmic reticulum isolated from rabbit skeletal muscle were investigated. The inhibitory effects of the cations on the enzyme activity increased as the concentrations of the ions increased with the order of efficiency of $Hg^{2+}$ > $Cu^{2+}$ > $Pb^{2+}$ > $Cd^{2+}$ > $Mn^{2+}$ in the concentration range between 10 and 500$\mu$M. The 50% inhibition for each ion was almost identical with the inhibition constant (Ki) value for each ion. The Ki's were 10, 30 130, and 350$\mu$M for $Hg^{2+}, Cu^{2+}, Pb^{2+}, and Cd^{2+}$, respectively. $Mn^{2+}$ seemed to be an activator at lower concentrations and an inhibitor at higher concentrations. The presence of the cations did not change the Km values, suggesting that the ions act as a reversible noncompetitive inhibitor on the FSR ATPase. The energy of activation of the enzyme was aproximately 19 Kcal/mole. The presence of the ions decreased the value slightly. A possible mechanism for the reversible noncompetitive inhibitory effect of the cations was discussed.

• The Journal of Korean Medicine
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• v.17 no.2 s.32
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• pp.264-276
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• 1996

This study was carried out to evaluate the effect of Samhwasan on the Na-K-ATPase activity of heart muscle. The Na-K-ATPase activity was prepared from rabbit heart ventricles. Samhwasan markedly inhibited the Na- K - ATPase activity in a dose-dependent manner with an estimated $I_{50}$ of 0.56%. Hill coefficient was 1.70, indicating that the enzyme has more than one binding site for the Samhwasan. Inhibition of enzyme activity by Samhwasan increased as pretreatment time was prolonged. Inhibition by the drug was not affected by a change in enzyme protein concentration. Kinetic studies of substrate activation of the enzyme indicated classical noncompetitive inhibition, showing significant reduction in Vmax without a change in Km value. Inhibitory effect by Samhwasan was not altered by changes in concentration of $Mg^{2+}$, $Na^+$ or $K^+$, dithiothreitol. a sulfhydryl reducing reagent, did not protect the inhibition of Na-K-ATPase activity by Samhwasan combination of Samhwasan and ouabain showed a cumulative inhibition fashion. These results suggest that Samhwasan inhibits Na-K-ATPase activity of heart ventricles with an unique binding site different from that of ATP, $Mg^{2+}$, $Na^+$ or $K^+$ and ouabain.

• International Journal of Oral Biology
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• v.36 no.2
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• pp.71-78
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• 2011

Using whole cell current- and voltage-clamp recording we investigated the characteristics and pharmacology of group I metabotropic glutamate receptor (mGluR)-mediated responses in rat medial vestibular nucleus (MVN) neurons. In current clamp conditions, activation of mGluR I by application of the group I mGluR agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) induced a direct excitation of MVN neurons that is characterized by depolarization and increased spontaneous firing frequency. To identify which of mGluR subtypes are responsible for the various actions of DHPG in MVN, we used two subtype-selective antagonists. (S)-(+)- alpha-amino-a-methylbenzeneacetic acid (LY367385) is a potent competitive antagonist that is selective for mGluR1, whereas 2-methyl-6-(phenylethynyl)-pyridine (MPEP) is a potent noncompetitive antagonist that is selective for mGluR5. In voltage clamp conditions, DHPG application increased the frequency of spontaneous and miniature inhibitory postsynaptic currents (IPSCs) but had no effect on amplitude distributions. Antagonism of the DHPG-induced increase of miniature IPSCs required the blockade of both mGluR1 and mGluR5. DHPG application induced an inward current, which can be enhanced under depolarized conditions. DHPG-induced current was blocked by LY367385, but not by MPEP. Both LY367385 and MPEP antagonized the DHPG-induced suppression of the calcium activated potassium current ($I_{AHP}$). These data suggest that mGluR1 and mGluR5 have similar roles in the regulation of the excitability of MVN neurons, and show a little distinct. Furthermore, mGluR I, via pre- and postsynaptic actions, have the potential to modulate the functions of the MVN.