Influence of Mg2+ ions on the interaction between 3,5-dicaffeoylquinic acid and HTLV-I integrase
Using molecular simulation, we studied the influence of Mg2+ ions on the binding mode of HTLV-I Integrase (IN) catalyticdomain (modeled by homology) with the 3,5- Dicaffeoylquinic Acid (DCQA). HTLV-I Integrase homology model was built usingtemplate-like crystallographic data of the IN catalytic doma...
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Pontificia Universidad Javeriana
2012-04-01
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| Series: | Universitas Scientiarum |
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| Online Access: | http://revistas.javeriana.edu.co/index.php/scientarium/article/view/2477/1756 |
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| author | Orlando Acevedo Yesid Cuesta-Astroz Juvenal Yosa Reyes Ángela Peña, Jesús Felipe García-Vallejo |
| author_facet | Orlando Acevedo Yesid Cuesta-Astroz Juvenal Yosa Reyes Ángela Peña, Jesús Felipe García-Vallejo |
| author_sort | Orlando Acevedo |
| collection | DOAJ |
| description | Using molecular simulation, we studied the influence of Mg2+ ions on the binding mode of HTLV-I Integrase (IN) catalyticdomain (modeled by homology) with the 3,5- Dicaffeoylquinic Acid (DCQA). HTLV-I Integrase homology model was built usingtemplate-like crystallographic data of the IN catalytic domain solved for Avian Sarcoma Virus (VSA, pdb: 1VSD). Materials andmethods. In order to analyze the role of Mg2+ in the interaction or coupling between 3,5-DCQA and Integrase, three models were created:i) in the absence of Mg2+ ions, ii) with a Mg2+ ion coordinated at Asp15 and Asp72 and iii) model with two Mg2+ ions coordinated atAsp15-Asp72 and Asp72-Glu108. Coupling force and binding free energy between 3,5-DCQA and HTLV-I IN were assessed in the threemodels. Results. The lowest docking score and free energy binding were obtained for the second model. Mg2+ ion strongly affected thecoupling of the inhibitor 3,5-DCQA with HTLV-I catalytic domain of Integrase, thus revealing a strong interaction in the ligand-proteincomplex regardless of the ligand-catalytic interaction sites for all three models. Conclusion. Altogether, these results strengthen thehypothesis that the presence of one Mg2+ ion could enhance the interaction in the complex by decreasing free energy, therefore increasing the affinity. Moreover, we propose 3, 5-DCQA as an important pharmacophore in the rational design of new antiretroviral drugs. |
| format | Article |
| id | doaj-art-eb5ed75b706449bca6744b10e30e336f |
| institution | DOAJ |
| issn | 0122-7483 2027-1352 |
| language | English |
| publishDate | 2012-04-01 |
| publisher | Pontificia Universidad Javeriana |
| record_format | Article |
| series | Universitas Scientiarum |
| spelling | doaj-art-eb5ed75b706449bca6744b10e30e336f2025-08-20T03:06:30ZengPontificia Universidad JaverianaUniversitas Scientiarum0122-74832027-13522012-04-01171515Influence of Mg2+ ions on the interaction between 3,5-dicaffeoylquinic acid and HTLV-I integraseOrlando AcevedoYesid Cuesta-AstrozJuvenal Yosa ReyesÁngela Peña,Jesús Felipe García-VallejoUsing molecular simulation, we studied the influence of Mg2+ ions on the binding mode of HTLV-I Integrase (IN) catalyticdomain (modeled by homology) with the 3,5- Dicaffeoylquinic Acid (DCQA). HTLV-I Integrase homology model was built usingtemplate-like crystallographic data of the IN catalytic domain solved for Avian Sarcoma Virus (VSA, pdb: 1VSD). Materials andmethods. In order to analyze the role of Mg2+ in the interaction or coupling between 3,5-DCQA and Integrase, three models were created:i) in the absence of Mg2+ ions, ii) with a Mg2+ ion coordinated at Asp15 and Asp72 and iii) model with two Mg2+ ions coordinated atAsp15-Asp72 and Asp72-Glu108. Coupling force and binding free energy between 3,5-DCQA and HTLV-I IN were assessed in the threemodels. Results. The lowest docking score and free energy binding were obtained for the second model. Mg2+ ion strongly affected thecoupling of the inhibitor 3,5-DCQA with HTLV-I catalytic domain of Integrase, thus revealing a strong interaction in the ligand-proteincomplex regardless of the ligand-catalytic interaction sites for all three models. Conclusion. Altogether, these results strengthen thehypothesis that the presence of one Mg2+ ion could enhance the interaction in the complex by decreasing free energy, therefore increasing the affinity. Moreover, we propose 3, 5-DCQA as an important pharmacophore in the rational design of new antiretroviral drugs.http://revistas.javeriana.edu.co/index.php/scientarium/article/view/2477/175635 -Dicaffeoylquinic AcidHuman T-Lymphotropic Type I (HTLV-1)Integrase (IN)Homology ModelMolecular DockingBinding Free EnergyMg2+ Ions. |
| spellingShingle | Orlando Acevedo Yesid Cuesta-Astroz Juvenal Yosa Reyes Ángela Peña, Jesús Felipe García-Vallejo Influence of Mg2+ ions on the interaction between 3,5-dicaffeoylquinic acid and HTLV-I integrase Universitas Scientiarum 3 5 -Dicaffeoylquinic Acid Human T-Lymphotropic Type I (HTLV-1) Integrase (IN) Homology Model Molecular Docking Binding Free Energy Mg2+ Ions. |
| title | Influence of Mg2+ ions on the interaction between 3,5-dicaffeoylquinic acid and HTLV-I integrase |
| title_full | Influence of Mg2+ ions on the interaction between 3,5-dicaffeoylquinic acid and HTLV-I integrase |
| title_fullStr | Influence of Mg2+ ions on the interaction between 3,5-dicaffeoylquinic acid and HTLV-I integrase |
| title_full_unstemmed | Influence of Mg2+ ions on the interaction between 3,5-dicaffeoylquinic acid and HTLV-I integrase |
| title_short | Influence of Mg2+ ions on the interaction between 3,5-dicaffeoylquinic acid and HTLV-I integrase |
| title_sort | influence of mg2 ions on the interaction between 3 5 dicaffeoylquinic acid and htlv i integrase |
| topic | 3 5 -Dicaffeoylquinic Acid Human T-Lymphotropic Type I (HTLV-1) Integrase (IN) Homology Model Molecular Docking Binding Free Energy Mg2+ Ions. |
| url | http://revistas.javeriana.edu.co/index.php/scientarium/article/view/2477/1756 |
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