Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations
Medium- and long-chain saturated and unsaturated free fatty acids (FFAs) are known to bind to human serum albumin (HSA), the main plasma carrier protein. Atomic-level structural data regarding the binding mode in Sudlow’s sites I (FA7) and II (FA4, FA3) of the polyunsaturated ω-3 fatty acids docosah...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/9/3724 |
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| author | Eleni Alexandri Themistoklis Venianakis Alexandra Primikyri Georgios Papamokos Ioannis P. Gerothanassis |
| author_facet | Eleni Alexandri Themistoklis Venianakis Alexandra Primikyri Georgios Papamokos Ioannis P. Gerothanassis |
| author_sort | Eleni Alexandri |
| collection | DOAJ |
| description | Medium- and long-chain saturated and unsaturated free fatty acids (FFAs) are known to bind to human serum albumin (HSA), the main plasma carrier protein. Atomic-level structural data regarding the binding mode in Sudlow’s sites I (FA7) and II (FA4, FA3) of the polyunsaturated ω-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), however, are largely unknown. Herein, we report the combined use of saturation transfer difference (STD) and Interligand NOEs for Pharmacophore Mapping (INPHARMA) NMR techniques and molecular docking calculations to investigate the binding mode of DHA and EPA in Sudlow’s sites Ι and ΙΙ of HSA. The docking calculations and the significant number of interligand NOEs between DHA and EPA and the drugs warfarin and ibuprofen, which are stereotypical ligands for Sudlow’s sites I and II, respectively, were interpreted in terms of competitive binding modes and the presence of two orientations of DHA and EPA at the binding sites FA7 and FA4. The exceptional flexibility of the long-chain DHA and EPA and the formation of strongly folded structural motives are the key properties of HSA–PUFA complexes. |
| first_indexed | 2024-03-11T04:12:30Z |
| format | Article |
| id | doaj.art-cae3848439c940b2b2a1fdaddfa627ce |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T04:12:30Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-cae3848439c940b2b2a1fdaddfa627ce2023-11-17T23:22:36ZengMDPI AGMolecules1420-30492023-04-01289372410.3390/molecules28093724Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking CalculationsEleni Alexandri0Themistoklis Venianakis1Alexandra Primikyri2Georgios Papamokos3Ioannis P. Gerothanassis4Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, GR-45110 Ioannina, GreeceSection of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, GR-45110 Ioannina, GreeceSection of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, GR-45110 Ioannina, GreeceSection of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, GR-45110 Ioannina, GreeceSection of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, GR-45110 Ioannina, GreeceMedium- and long-chain saturated and unsaturated free fatty acids (FFAs) are known to bind to human serum albumin (HSA), the main plasma carrier protein. Atomic-level structural data regarding the binding mode in Sudlow’s sites I (FA7) and II (FA4, FA3) of the polyunsaturated ω-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), however, are largely unknown. Herein, we report the combined use of saturation transfer difference (STD) and Interligand NOEs for Pharmacophore Mapping (INPHARMA) NMR techniques and molecular docking calculations to investigate the binding mode of DHA and EPA in Sudlow’s sites Ι and ΙΙ of HSA. The docking calculations and the significant number of interligand NOEs between DHA and EPA and the drugs warfarin and ibuprofen, which are stereotypical ligands for Sudlow’s sites I and II, respectively, were interpreted in terms of competitive binding modes and the presence of two orientations of DHA and EPA at the binding sites FA7 and FA4. The exceptional flexibility of the long-chain DHA and EPA and the formation of strongly folded structural motives are the key properties of HSA–PUFA complexes.https://www.mdpi.com/1420-3049/28/9/3724HSADHAEPASTD NMRINPHARMA NMRdocking calculations |
| spellingShingle | Eleni Alexandri Themistoklis Venianakis Alexandra Primikyri Georgios Papamokos Ioannis P. Gerothanassis Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations Molecules HSA DHA EPA STD NMR INPHARMA NMR docking calculations |
| title | Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations |
| title_full | Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations |
| title_fullStr | Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations |
| title_full_unstemmed | Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations |
| title_short | Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations |
| title_sort | molecular basis for the selectivity of dha and epa in sudlow s drug binding sites in human serum albumin with the combined use of nmr and docking calculations |
| topic | HSA DHA EPA STD NMR INPHARMA NMR docking calculations |
| url | https://www.mdpi.com/1420-3049/28/9/3724 |
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