Molecular recognition of two bioactive coumarin derivatives 7-hydroxycoumarin and 4-methyl-7-hydroxycoumarin by hen egg white lysozyme : Exploring the binding mechanism, thermodynamic parameters and structural changes using multispectroscopic and computational approaches
Multispectroscopic and computational methods of exploring the interaction between a carrier protein and therapeutic compounds provide a preliminary investigation into establishing the efficacy of such compounds. Here, two coumarin derivatives, 7-hydroxycoumarin (7-HC) and 4-methyl-7-hydroxycoumarin (4-Me-7-HC), were selected to carry out numerous biophysical interaction studies with a model carrier protein, hen egg white lysozyme (HEWL). Fluorescence spectroscopy studies conducted between HEWL and 7-HC/4-Me-7-HC revealed the binding constants (Kb) were in the range of 104 M-1, indicating a moderate nature of binding. The quenching mechanism observed during complexation process was an unusual static quenching due to the effect of temperature on the rate constant. Thermodynamic parameters revealed a positive ΔH and ΔS for HEWL-7-HC/4-Me-7-HC, indicating hydrophobic forces played a dominant role in the interaction process. FRET studies suggested a possible non-radiative energy transfer from the donor (HEWL) to the acceptor (coumarins). Molecular docking studies revealed the interaction of 7-HC/4-Me-7-HC with intrinsic fluorophores, Trp63 and Trp108, Trp108 being an essential residue for binding as proven by molecular dynamic (MD) simulation. MD simulation studies also indicated conformational stability gained by HEWL upon interaction with 7-HC and 4-Me-7-HC. The microenvironment surrounding the Trp residues showed a significant Stoke's shift on carrying out 3-D fluorescence. CD studies revealed a decrease in the alpha helical content of HEWL upon interacting with the ligands. Enzymatic assay conducted for HEWL in the presence of 7-HC/4-Me-7-HC saw an increase in the activity of HEWL, suggesting a change in structural conformation and stability of the protein, altering its activity.Communicated by Ramaswamy H. Sarma.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
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| Enthalten in: |
Journal of biomolecular structure & dynamics - 40(2022), 24 vom: 01., Seite 13872-13888 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lyndem, Sona [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.12.2022 Date Revised 28.02.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/07391102.2021.1995499 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Lyndem, Sona |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Molecular recognition of two bioactive coumarin derivatives 7-hydroxycoumarin and 4-methyl-7-hydroxycoumarin by hen egg white lysozyme |b Exploring the binding mechanism, thermodynamic parameters and structural changes using multispectroscopic and computational approaches |
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| 500 | |a Date Revised 28.02.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Multispectroscopic and computational methods of exploring the interaction between a carrier protein and therapeutic compounds provide a preliminary investigation into establishing the efficacy of such compounds. Here, two coumarin derivatives, 7-hydroxycoumarin (7-HC) and 4-methyl-7-hydroxycoumarin (4-Me-7-HC), were selected to carry out numerous biophysical interaction studies with a model carrier protein, hen egg white lysozyme (HEWL). Fluorescence spectroscopy studies conducted between HEWL and 7-HC/4-Me-7-HC revealed the binding constants (Kb) were in the range of 104 M-1, indicating a moderate nature of binding. The quenching mechanism observed during complexation process was an unusual static quenching due to the effect of temperature on the rate constant. Thermodynamic parameters revealed a positive ΔH and ΔS for HEWL-7-HC/4-Me-7-HC, indicating hydrophobic forces played a dominant role in the interaction process. FRET studies suggested a possible non-radiative energy transfer from the donor (HEWL) to the acceptor (coumarins). Molecular docking studies revealed the interaction of 7-HC/4-Me-7-HC with intrinsic fluorophores, Trp63 and Trp108, Trp108 being an essential residue for binding as proven by molecular dynamic (MD) simulation. MD simulation studies also indicated conformational stability gained by HEWL upon interaction with 7-HC and 4-Me-7-HC. The microenvironment surrounding the Trp residues showed a significant Stoke's shift on carrying out 3-D fluorescence. CD studies revealed a decrease in the alpha helical content of HEWL upon interacting with the ligands. Enzymatic assay conducted for HEWL in the presence of 7-HC/4-Me-7-HC saw an increase in the activity of HEWL, suggesting a change in structural conformation and stability of the protein, altering its activity.Communicated by Ramaswamy H. Sarma | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a 7-hydroxycoumarin | |
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| 700 | 1 | |a Jana, Madhurima |e verfasserin |4 aut | |
| 700 | 1 | |a Belwal, Vinay Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Singha Roy, Atanu |e verfasserin |4 aut | |
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