• Journal of Microbiology and Biotechnology
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• v.9 no.1
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• pp.119-121
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• 1999

Tumor cell interaction with the extracellular matrix is defined as the critical event of tumor invasion that signals the initiation of a metastatic cascade. Sesquicillin has been identified as an inhibitor of melanoma cell adhesion to the components of the extracellular matrix (ECM) in cultured broth of fungal strain F60063. Sesquicillin strongly inhibited the adhesion of B16 melanoma cells to laminin, fibronectin, and typeIV collagen. It also inhibited B16 melanoma cell invasion of reconstituted basement membrane Matrigel in vitro in a dose-dependent manner. These results suggest that sesquicillin is a new class of nonpeptidic ECM adhesion inhibitor having anti-invasive activity.

• The Journal of Korean Medicine
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• v.16 no.1 s.29
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• pp.281-294
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• 1995

The effect of Sam Hwa San on the Na-K-ATPase activity was evaluated in microsomal fraction prepared from rabbit cerebral cortex to determine whether Sam Hwa San affects Na-K-ATPase activity of nervous system. Sam Hwa San markedly inhibited the Na-K-ATPase activity in a dose-dependent manner with an estimated $I_{50}$ of 0.12%. Optimal pH for the Na-K-ATPase activity was at 7.5 in the presence or absence of Sam Hwa San. The degree of inhibition by the drug more increased at acidic and alkalic pHs than neutral pH. Kinetic studies of substrate and cationic activation of the enzyme indicate classic noncompetitive inhibition fashion for ATP, Na and K, showing significant reduction in Vmax without a change in Km. Dithiothreitol, a sulfhydryl reducing reagent, partially protects the inhibition of Na-K-ATPase activity by Sam Hwa San. Combination of Sam Hwa San and ouabain showed higher inhibition than cumulative inhibition. These results suggest that Sam Hwa San inhibits Na-K-ATPase activity in central nervous system by reacting with, at least a part, sulfhydryl group and ouabain binding site of the enzyme protein, but with different binding site from those of ATP, Na and K.

• YAKHAK HOEJI
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• v.44 no.1
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• pp.47-51
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• 2000

To examine whether DGRF inhibits $cPLA_2$ activity in vitro, we purified a 100 kDa $cPLA_2$enzyme from porcine spleen and performed an inhibition study at two concentrations of 5.0 and 50.0 $\mu$M 1-stearoyl-2-[1-$^{l4C}$ ]arachidonoyl-sn -glycero-3-phosphocholine as a substrate to rule out an apparent inhibition due to "substrate depletion". Here we reported that DGRF inhibited $cPLA_2$activity with $ID_{50}$ of 3.2 $\mu$M and virtually complete inactivation of the enzyme occurred at 60 $\mu$M. Interaction experiment between enzyme protein and inhibitor by ultrafiltration method indicated that 1-desgalloylrugosin-F inactivates $cPLA_2$enzyme by an irreversible mechanism.

• Korean Journal of Microbiology
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• v.29 no.2
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• pp.97-103
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• 1991

Glutamine phosphoribosylpyrophosphate amidotransferase of Streptomyces tubercidicus was purified and characterized. Molecular weight of the isolated enzyme was determined to be approximately 230,000 and was composed foru identical subunits having a molecular weight of 58,000. This enzyme was strongly inhibited by AMP while considerably inhibited by ATP and GTP. Inhibition effect of enzyme activity by AMP was antagonized by increased concentration of substrate, PRPP, and metal ion (especially, $Mg^{++}$) was essential in both catalytic activity and nucleotide inhibition of this enzyme. Therefore, it was confirmed that end product inhibition of glutamine phosphoribosylpyrophosphate amidotransferase by adenine participated in the regulation of tubercidin biosynthesis from Streptomyces tubercidicus.s.

• BMB Reports
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• v.31 no.5
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• pp.459-467
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• 1998

A new set of functional group interaction energy descriptors relevant to the ACE (Angiotensin-Converting Enzyme) inhibitory peptide, QSAR (Quantitative Structure Activity Relationships), is presented. The functional group interaction energies approximate the charged interactions and distances between functional groups in molecules. The effective energies of the computationally derived geometries are useful parameters for deriving 3D-QSAR models, especially in the absence of experimentally known active site conformation. ACE is a regulatory zinc protease in the renin-angiotensin system. Therapeutic inhibition of this enzyme has proven to be a very effective treatment for the management of hypertension. The non bond interaction energy values among functional groups of six-feature of ACE inhibitory peptides were used as descriptor terms and analyzed for multivariate correlation with ACE inhibition activity. The functional group interaction energy descriptors used in the regression analysis were obtained by a series of inhibitor structures derived from molecular mechanics and semi-empirical calculations. The descriptors calculated using electrostatic and steric fields from the precisely defined functional group were sufficient to explain the biological activity of inhibitor. Application of the descriptors to the inhibition of ACE indicates that the derived QSAR has good predicting ability and provides insight into the mechanism of enzyme inhibition. The method, functional group interaction energy analysis, is expected to be applicable to predict enzyme inhibitory activity of the rationally designed inhibitors.

• Korean Journal Plant Pathology
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• v.10 no.2
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• pp.119-122
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• 1994

Effects of organophosphorus fungicides on cutinase activity from Glomerella cingulata causing apple anthracnose and infection of apple were investigated. Diisoprophylfluorophosphate (DFP) inhibited the enzyme activity indicating that catalysis involves an active serine. In inhibition of the enzyme activity by organophosphorus fungicides, I50 (molar concentration of fungicide at which the enzyme activity is inhibited 50%) of Hinosan and Kitazin P were 26.3 $\mu$M and 427.7 $\mu$M, respectively. At concentration of 10-3 M DFP and organophosphorus fungicides, the infection of G. cingulata was inhibited to 5% in comparison with 15% infection at the unwounded healthy control, but increased to 30% when added with 1 mg/ml of cutinase. Mycelial growth was 36 mm in colony diameter on the medium added with 10-4M of hinosan in comparison with 90 mm of the untreated control, but was 90 mm on the medium added with 10-4M of kitazin P showing lower inhibition than hinosan. The spore germination was more than 60% at all the concentrations of both fungicides.

• Journal of Environmental Science International
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• v.7 no.1
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• pp.52-56
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• 1998

The effects of organophosphorus and carbamate pesticides were examined inhibition of the acetylcholinesterase activity in the chicken brain with enzyme-inhibition methods. The acetylcholinesterase activity in chicken brain determined by the Ellman method was 167 mmol/min/g protein. The optimum pH of acetycholinesterase was 8.2. $pl_{50}$ of acetycholinesterase by some organophosphorus were 3.80M of phosphorodlthioate, 4.04M of phosphorothioate, 6.33M of phosphate, and 6.60M of phosphrothiolate. pluto of acetycholinesterase by some carbamates were 5.1 OM of XMC, 5. 90M of carbofuran, 6.16M of isoprocarb, 6.30M of carbaryl, 6.47M of BPMC, and 6.77M of propoxur. pluto of carbamates selected was similar to that of phosphorothioate and phosphate organophosphates.

• Journal of Microbiology and Biotechnology
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• v.9 no.4
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• pp.414-421
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• 1999

Helicobacter pylori were found to be resistant to azide but sensitive to vanadate, suggesting that defect in the P-type ATPase activity rather than F-type ATPase would be lethal to cell survival or growth. To elucidate the relationship between this enzyme inhibition and H. pylori death, we determined the effect of omeprazole (OMP) plus vanadate on enzyme activity and cell growth. The minimum inhibitory concentration (MIC; ca. 0.8$\mu$mol/disk) of vanadate for H. pylori growth was lowered over l0-fold with the aid of OMP, whereby its inhibitory potential toward the P-type ATPase activity was diametrically increased. Alternatively, we found that this enzyme activity was essential for active transport in H. pylori. From these observations, we strongly suggest that the immediate cause of the growth inhibition of H. pylori cells with OMP and/or vanadate might be defective in the cell's active transport due to the lack of P-type ATPase activity. From the spectral data with circular dichroism (CD) spectroscopy, we found that activated OMP (OAS) at concentration below MIC did not disrupt helical structures of membrane proteins. Separately, we determined the cytopathic effect of OAS by SDS-PAGE, indicating the change in the production of cytoplasmic protein but not cell membrane.

• Bulletin of the Korean Chemical Society
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• v.30 no.11
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• pp.2523-2531
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• 2009

Effects of some diacid, diamine and dinitro aromatic compounds on the structure and activity of adenosine deaminase (ADA) were investigated by UV-Vis spectrophotometry in 50 mM phosphate buffer at pH = 7.5 and 27 ${^{\circ}C}$ and molecular docking studies. The results showed that all tested ligands are showing inhibition; five ligands are uncompetitive and other two ligands are mixed of competitive and noncompetetive inhibitors with majority of competitive behavior. For the later case analysis was done based on competitive inhibition. Diacids have larger size and higher inhibition constant ($K_I$) relative to others. A logical correlation between calculated free energy of binding and experimental values was obtained for un-competitive. Experimental and calculated data showed that competitive inhibitors are distributed near the active site of enzyme and form several cluster of ranks, whereas uncompetitive inhibitors bind to the enzyme-substrate complex and distributed far from the active site. Results of structure-activity relationship showed that, larger, more hydrophobe, less spherical and more aromatic ligands have higher inhibition constants.

• Journal of Plant Biology
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• v.30 no.4
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• pp.249-255
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• 1987

The effect of polyamine and Ca2+ on D-glucose-6-phosphate cyclohydrolase activity was studied in Daucus carota root. The enzyme activity was reduced in response to increase in concentration of Ca2+, not the Ca2+-calmodulin complex. The inhibition effect due to Ca2+ was reversed by polyamine, especially remarkable at low concentration of Ca2+. The effect of the Ca2+ on the enzyme seemed to compete with polyamine according to the Lineweaver-Burk plot. The enzyme activity from carrot root protoplast cultured in the prescence of verapamil was higher than that of the control. Such cumulative results suggest that the inhibition by the Ca2+ and enhancement or reversal by polyamine could regulate the biosynthesis of pectin and hemicellulose to some extent.