Spectroscopic and Docking Studies on the Binding of Liquiritigenin with Hyaluronidase for Antiallergic Mechanism

The inhibitory effect of liquiritigenin on hyaluronidase and its binding mechanism were investigated systematically by UV-vis absorption, fluorescence, and molecular modeling approaches. These results indicated that liquiritigenin could interact with hyaluronidase to form a liquiritigenin-hyaluronidase complex. The binding constant, number of binding sites, and thermodynamic parameters were calculated, which indicated that liquiritigenin could spontaneously bind with hyaluronidase mainly through electrostatic and hydrophobic interactions with one binding site. Synchronous fluorescence, three-dimensional fluorescence, and molecular docking results revealed that liquiritigenin bound directly to the enzyme cavity site and this binding influenced the microenvironment of the hyaluronidase activity site, resulting in reduced hyaluronidase activity. The present study provides useful information for clinical applications of liquiritigenin as a hyaluronidase inhibitor.

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The inhibitory Effects of Some Artificial Food Colorings on α-amylase and α-glucosidase: In Vitro and In Silico Studies

Current Enzyme Inhibition ◽

10.2174/1573408017666211018102605 ◽

2021 ◽

Vol 17 ◽

Author(s):

Reguia Mahfoudi ◽

Amar Djeridane ◽

Djilali Tahri ◽

Mohamed Yousfi

Keyword(s):

In Silico ◽

Hydrophobic Interactions ◽

Inhibitory Effect ◽

Docking Studies ◽

Qsar Study ◽

Molegro Virtual Docker ◽

Artificial Food ◽

In Silico Studies ◽

Ic50 Values

Background: Inhibition of α-amylase and α-glucosidase is considered as an important therapeutic target to manage type 2 diabetes mellitus (T2DM), reducing postprandial hyperglycemia (PPHG). Objective: The present work explored the antidiabetic activities of five artificial food colorings by α-amylase and α-glucosidase enzyme inhibition in vitro and in Silico. Methods: In this study, inhibition of α-amylase and α-glucosidase were evaluated. Further, the interaction between enzymes (α-amylase and α-glucosidase) and ligands (food colorings) was followed by QSAR and molecular docking studies. Results: The in vitro results obtained show that the blue patent (SIN131) exhibited more potent inhibition with IC50 values of 0.03± 0.01 mM and 0.014±0.001 mM against α-amylase and α-glucosidase inhibition respectively compared to acarbose. The QSAR study found a strong correlation between IC50 values with four molecular descriptors. This linear regression confirms that a strong polarity (Apol) and a low hydrophobia (ALogP) favor the inhibitory effect of these colorings toward both enzymes. Also, a negative role of the number of heavy atoms has been demonstrated in the phenomenon of inhibition of this enzyme. Finally, the descriptor εlumo (electronic affinity) plays a crucial role on the inhibitory power of these dyes toward both enzymes by electron transfer. The virtual screening of the inhibition of α-amylase and α-glucosidase by these colorings, using Molegro Virtual Docker (MVD), allowed us to obtain stable complexes with interaction energies resulting from the place of hydrogen bonds and several hydrophobic interactions. However, the sulfonate groups of these colorings can be the major factors in the inhibition of these enzymes. On the other hand, Rerank Score with the pose are perfectly correlated (R2> 0.76) to the inhibitory activity of these food colorings measured experimentally. Conclusion: The present study suggests that the Blue Patent V (SIN131) effectively act as α-amylase and α-glucosidase inhibitor leading to a reduction in starch hydrolysis and hence eventually to lowered glucose levels.

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Influence of surfactants on the fading of malachite green

Open Chemistry ◽

10.2478/s11532-007-0066-0 ◽

2008 ◽

Vol 6 (1) ◽

pp. 89-92 ◽

Cited By ~ 9

Author(s):

Adina Raducan ◽

Alexandra Olteanu ◽

Mihaela Puiu ◽

Dumitru Oancea

Keyword(s):

Malachite Green ◽

Anionic Surfactant ◽

Cationic Surfactants ◽

Hydrophobic Interactions ◽

Sodium Dodecyl ◽

Inhibitory Effect ◽

Dimethyl Ammonium Chloride ◽

Electrostatic And Hydrophobic Interactions ◽

Dimethyl Ammonium ◽

Kinetics Of

AbstractThe kinetics of the reaction between malachite green (MG) and sodium hydroxide (MG fading) was studied using a spectrophotometric method in the presence of two cationic surfactants, cetyl-benzyl-dimethyl-ammonium chloride (CBDAC) and hexadecyl-trimethylammonium bromide (HTAB) and one anionic surfactant, sodium dodecyl sulphate (SDS) at concentrations below and above critical micellar concentrations. The cationic surfactants have a catalytic effect, while the anionic surfactant has an inhibitory effect on the reaction. A kinetic model describing the influence of surfactant on reaction rate was developed. The results are discussed on the basis of electrostatic and hydrophobic interactions between the kinetic micelles and malachite green.

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Conservation of cofactor pockets in proteins

Acta Crystallographica Section A Foundations and Advances ◽

10.1107/s2053273314084848 ◽

2014 ◽

Vol 70 (a1) ◽

pp. C1515-C1515

Author(s):

Neela Yennawar ◽

Julia Fecko ◽

Rani Chapla

Keyword(s):

Functional Groups ◽

Active Site ◽

Hydrophobic Interactions ◽

Three Dimensional ◽

Systematic Assessment ◽

Protein Residues ◽

Enzyme Reactions ◽

Electrostatic And Hydrophobic Interactions ◽

Distance Matrices ◽

Enzyme Cofactors

Enzymes, organic cofactors and metal ions are crucial for many biochemical reactions for catalysis. Nearly half of all enzyme reactions are catalyzed by cofactors. So far a systematic assessment of the enzyme residues interacting with organic enzyme cofactors in biocatalysts has not been performed. Here, we analyze the environment, physicochemical nature and pockets of thirty organic cofactors. The cofactor pocket and residues lining it share a remarkable degree of structural convergence despite the rest of the protein having different three-dimensional folds and different enzymatic functions. There is a common network of electrostatic and hydrophobic interactions stabilizing the cofactors. Functional groups of cofactors have complementary charge interactions with polar residues in the active site. Rings are positioned in snug nonpolar pockets either completely or partially. Distance matrices have been derived for each of the cofactor pockets based on the protein residues interacting with functional groups. These distance matrices and the representative pocket sizes of cofactor can be used as a fingerprint to identify a cofactor pocket. Examples of proteins from the PDB classified as with unknown function have been screened for the derived cofactor pocket criteria.

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Influence of Concanavalin A, wheat germ agglutinin, and soybean agglutinin on the fusion of myoblasts in vitro.

The Journal of Cell Biology ◽

10.1083/jcb.67.3.826 ◽

1975 ◽

Vol 67 (3) ◽

pp. 826-834 ◽

Cited By ~ 42

Author(s):

H Den ◽

D A Malinzak ◽

H J Keating ◽

A Rosenberg

Keyword(s):

Concanavalin A ◽

Binding Sites ◽

Wheat Germ Agglutinin ◽

Wheat Germ ◽

Inhibitory Effect ◽

Myoblast Fusion ◽

Normal Serum ◽

Specific Cell ◽

Number Of Binding Sites

Although muscle cell fusion was shown to be an energy-requiring process, release of myoblasts from an EGTA fusion block could be accomplished with Earle's balanced salt solution (containing 1.8 mM Ca++) free of glucose or any other energy-produced metabolite. The effect of concanavalin A, abrin, and the lectins from wheat germ, soybean, and Lens culinaris on myoblast fusion was examined with synchronized myoblast cultures upon release from fusion block. At a concentration of 15 mug/ml, these lectins were found to inhibit the fusion process to the extent of 62%, 41%, 32%, 8%, and 19%, respectively. Concanavalin A inhibition could be prevented by alpha-methyl-D-mannoside. The inhibitory effect of all the lectins except abrin could be reversed by changing to the normal, serum-containing medium. The number of binding sites was 3.4 X 10(7), 6.1 X 10(7), and 1.7 X 10(6), respectively. Although myoblasts were found to have about twice as many binding sites for wheat germ agglutinin as for concanavalin A, concanavalin A was determined to be twice as effective as wheat germ agglutinin as an inhibitor of myoblast fusion. These findngs raise the possibility that specific cell surface glycoproteins may be an important factor in this process.

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Discovery of 3-Arylquinoxaline Derivatives as Potential Anti-Dengue Virus Agents

International Journal of Molecular Sciences ◽

10.3390/ijms20194786 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4786

Author(s):

Chih-Hua Tseng ◽

Cheng-Ruei Han ◽

Kai-Wei Tang

Keyword(s):

Dengue Virus ◽

Messenger Rna ◽

Active Sites ◽

Hydrophobic Interactions ◽

Biological Activities ◽

Inhibitory Effect ◽

Docking Studies ◽

Mrna Levels ◽

Dependent Manner ◽

Cox 2

We designed and synthesized a series of novel 3-arylquinoxaline derivatives and evaluated their biological activities as potential dengue virus (DENV) replication inhibitors. Among them, [3-(4-methoxyphenyl)quinoxalin-2-yl](phenyl)methanol (19a), [6,7-dichloro-3-(4-methoxyphenyl)quinoxalin-2-yl](phenyl)methanol (20a), and (4-methoxyphenyl)(3-phenylquinoxalin-2-yl)methanone (21b) were found to significantly inhibit the DENV RNA expression in Huh-7-DV-Fluc cells with a potency better than that of ribavirin. Compound 19a reduced DENV replication in both viral protein and messenger RNA (mRNA) levels in a dose-dependent manner and exhibited no significant cell cytotoxicity. Notably, compound 19a exhibited a half maximal effective concentration (EC50) value at 1.29 ± 0.74 μM. We further observed that the inhibitory effect of 19a on DENV replication was due to suppression of DENV-induced cyclooxygenase-2 (COX-2) expression. Docking studies also showed that 19a caused hydrophobic interactions at the active sites with Arg29, Glu31, Tyr116, Leu138, Pro139, Lys454, Arg455, and Gln529. The calculated lowest binding energy between the 19a and COX-2 was −9.10 kcal/mol. In conclusion, compound 19a might be a potential lead compound for developing an anti-DENV agent.

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Conformation of Ribosomes from Escherichia Coli

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100051062 ◽

1974 ◽

Vol 32 ◽

pp. 210-211

Author(s):

M. Boublik ◽

W. Hellmann ◽

F. Jenkins

Keyword(s):

Binding Sites ◽

Ribosomal Proteins ◽

Fluorescent Dyes ◽

Protein Biosynthesis ◽

Three Dimensional ◽

Spatial Arrangement ◽

Dimensional Structure ◽

Complete Understanding ◽

And Function

The present knowledge of the three-dimensional structure of ribosomes is far too limited to enable a complete understanding of the various roles which ribosomes play in protein biosynthesis. The spatial arrangement of proteins and ribonuclec acids in ribosomes can be analysed in many ways. Determination of binding sites for individual proteins on ribonuclec acid and locations of the mutual positions of proteins on the ribosome using labeling with fluorescent dyes, cross-linking reagents, neutron-diffraction or antibodies against ribosomal proteins seem to be most successful approaches. Structure and function of ribosomes can be correlated be depleting the complete ribosomes of some proteins to the functionally inactive core and by subsequent partial reconstitution in order to regain active ribosomal particles.

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The Estimation of the Number of Binding Sites for Antibody on Antigen Molecules with Reference to Factor VIII and its Antibody

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647956 ◽

1976 ◽

Vol 35 (02) ◽

pp. 274-288 ◽

Cited By ~ 2

Author(s):

Judith Pool ◽

Rosemary Biggs ◽

R. G Miller

Keyword(s):

Factor Viii ◽

Binding Sites ◽

Theoretical Basis ◽

Human Antibody ◽

Rabbit Antibody ◽

Number Of Binding Sites ◽

Theoretical Considerations

SummaryThe theoretical basis for determining the number of antibody sites on antigen molecules is examined. The theoretical considerations are applied to factor VIII molecules. Examples based on data available at the Oxford Haemophilia Centre are calculated to illustrate the approach. It is concluded that there are few sites on each factor VIII molecule for human antibody. The three antibodies for which reasonable data were available suggest 1–3 sites for human antibody. The data for rabbit antibody suggest 5–6 sites per factor VIII molecule.

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Characterization of Thromboxane A2/Prostaglandin H2 Receptors in Porcine Coronary Artery -The Inhibitory Effect of a Novel Dibenzoxepin Derivative, KW-3635

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648498 ◽

1992 ◽

Vol 67 (05) ◽

pp. 582-584 ◽

Cited By ~ 2

Author(s):

Ichiro Miki ◽

Akio Ishii

Keyword(s):

Coronary Artery ◽

Binding Sites ◽

Thromboxane A2 ◽

Inhibitory Effect ◽

Scatchard Analysis ◽

Single Class ◽

Porcine Coronary Artery ◽

Equilibrium Binding ◽

H2 Receptors

SummaryWe characterized the thromboxane A2/prostaglandin H2 receptors in porcine coronary artery. The binding of [3H]SQ 29,548, a thromboxane A2 antagonist, to coronary arterial membranes was saturable and displaceable. Scatchard analysis of equilibrium binding showed a single class of high affinity binding sites with a dissociation constant of 18.5 ±1.0 nM and the maximum binding of 80.7 ± 5.2 fmol/mg protein. [3H]SQ 29,548 binding was concentration-dependently inhibited by thromboxane A2 antagonists such as SQ 29,548, BM13505 and BM13177 or the thromboxane A2 agonists such as U46619 and U44069. KW-3635, a novel dibenzoxepin derivative, concentration-dependently inhibited the [3H]SQ 29,548 binding to thromboxane A2/prosta-glandin H2 receptors in coronary artery with an inhibition constant of 6.0 ± 0.69 nM (mean ± S.E.M.).

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Abnormal Platelet Serotonin Uptake and Binding Sites in Myeloproliferative Disorders

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661099 ◽

1984 ◽

Vol 51 (03) ◽

pp. 349-353 ◽

Cited By ~ 9

Author(s):

C Caranobe ◽

P Sié ◽

F Fernandez ◽

J Pris ◽

S Moatti ◽

...

Keyword(s):

Binding Sites ◽

High Capacity ◽

Specific Inhibitor ◽

Myeloproliferative Disorders ◽

Normal Subjects ◽

Binding Data ◽

Full Explanation ◽

Number Of Binding Sites ◽

5 Ht Uptake ◽

Kinetics Of

SummaryA simultaneous investigation of the kinetics of serotonin (5 HT) uptake and of binding sites was carried out in the platelets of normal subjects and of 10 patients affected with various types of myeloproliferative disorders (MD). The 5 HT uptake was analysed according to the Lineweaver-Burk and the Eadie-Hofstee methods. With the two methods, the patient’s platelets exhibited a dramatic reduction of the Vi max and of the Km; in some patients the Eadie-Hofstee analysis revealed that a passive diffusion phenomenon is superimposed on the active 5 HT uptake at least for the higher concentration used. The binding data were analysed with the Scatchard method. Two classes of binding sites (high affinity - low capacity, low affinity - high capacity) were found in normal subjects and patients. Pharmacological studies with imipramine, a specific inhibitor of 5 HT uptake, suggested that both the sites are involved in 5 HT uptake. The number of both binding sites was significantly decreased in patient’s platelets while the affinity constants of these binding sites were not significantly reduced in comparison with those of the control subjects. No correlations were found between Vi max, Km and the number of binding sites. These results suggest that a reduction in the number of platelet membrane acceptors for 5 HT commonly occurs in myeloproliferative disorders but does not provide a full explanation of the uptake defect.

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Functional Involvement of Thrombospondin in Platelet Aggregation Induced by Low Versus High Concentrations of Thrombin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661464 ◽

1986 ◽

Vol 55 (01) ◽

pp. 136-142 ◽

Cited By ~ 4

Author(s):

K J Kao ◽

David M Shaut ◽

Paul A Klein

Keyword(s):

Platelet Aggregation ◽

Binding Sites ◽

Inhibitory Effect ◽

Activated Platelets ◽

Low Concentrations ◽

Platelet Binding ◽

Functional Involvement ◽

Thrombin Activation ◽

Platelet Aggregates ◽

High Concentrations

SummaryThrombospondin (TSP) is a major platelet secretory glycoprotein. Earlier studies of various investigators demonstrated that TSP is the endogenous platelet lectin and is responsible for the hemagglutinating activity expressed on formaldehyde-fixed thrombin-treated platelets. The direct effect of highly purified TSP on thrombin-induced platelet aggregation was studied. It was observed that aggregation of gel-filtered platelets induced by low concentrations of thrombin (≤0.05 U/ml) was progressively inhibited by increasing concentrations of exogenous TSP (≥60 μg/ml). However, inhibition of platelet aggregation by TSP was not observed when higher than 0.1 U/ml thrombin was used to activate platelets. To exclude the possibility that TSP inhibits platelet aggregation by affecting thrombin activation of platelets, three different approaches were utilized. First, by using a chromogenic substrate assay it was shown that TSP does not inhibit the proteolytic activity of thrombin. Second, thromboxane B2 synthesis by thrombin-stimulated platelets was not affected by exogenous TSP. Finally, electron microscopy of thrombin-induced platelet aggregates showed that platelets were activated by thrombin regardless of the presence or absence of exogenous TSP. The results indicate that high concentrations of exogenous TSP (≥60 μg/ml) directly interfere with interplatelet recognition among thrombin-activated platelets. This inhibitory effect of TSP can be neutralized by anti-TSP Fab. In addition, anti-TSP Fab directly inhibits platelet aggregation induced by a low (0.02 U/ml) but not by a high (0.1 U/ml) concentration of thrombin. In conclusion, our findings demonstrate that TSP is functionally important for platelet aggregation induced by low (≤0.05 U/ml) but not high (≥0.1 U/ml) concentrations of thrombin. High concentrations of exogenous TSP may univalently saturate all its platelet binding sites consequently interfering with TSP-crosslinking of thrombin-activated platelets.

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