Structural Basis of Artemisinin Binding Sites in Serum Albumin with the Combined Use of NMR and Docking Calculations

Artemisinin is known to bind to the main plasma protein carrier serum albumin (SA); however, there are no atomic level structural data regarding its binding mode with serum albumin. Herein, we employed a combined strategy of saturation transfer difference (STD), transfer nuclear Overhauser effect spectroscopy (TR-NOESY), STD–total correlation spectroscopy (STD-TOCSY), and Interligand Noes for PHArmacophore Mapping (INPHARMA) NMR methods and molecular docking calculations to investigate the structural basis of the interaction of artemisinin with human and bovine serum albumin (HSA/BSA). A significant number of inter-ligand NOEs between artemisinin and the drugs warfarin and ibuprofen as well as docking calculations were interpreted in terms of competitive binding modes of artemisinin in the warfarin (FA7) and ibuprofen (FA4) binding sites. STD NMR experiments demonstrate that artemisinin is the main analyte for the interaction of the A. annua extract with BSA. The combined strategy of NMR and docking calculations of the present work could be of general interest in the identification of the molecular basis of the interactions of natural products with their receptors even within a complex crude extract.

[1]  Apostolos Avgeropoulos,et al.  NMR and computational studies reveal novel aspects in molecular recognition of unsaturated fatty acids with non‐labelled serum albumin , 2022, The FEBS journal.

[2]  I. Gerothanassis,et al.  Analytical and Structural Tools of Lipid Hydroperoxides: Present State and Future Perspectives , 2022, Molecules.

[3]  J. Vacek,et al.  Serum albumin as a primary non-covalent binding protein for nitro-oleic acid , 2022, International Journal of Biological Macromolecules.

[4]  J. Bukh,et al.  In vitro efficacy of artemisinin-based treatments against SARS-CoV-2 , 2020, Scientific Reports.

[5]  Zhìhóng Hú,et al.  Anti-SARS-CoV-2 Potential of Artemisinins In Vitro , 2020, ACS infectious diseases.

[6]  I. Gerothanassis,et al.  Simultaneous determination of artemisinin and its analogs and flavonoids in Artemisia annua crude extracts with the use of NMR spectroscopy , 2019, Magnetic resonance in chemistry : MRC.

[7]  R. Guzzi,et al.  Warfarin increases thermal resistance of albumin through stabilization of the protein lobe that includes its binding site. , 2019, Archives of biochemistry and biophysics.

[8]  Li-Ke Xie,et al.  More than anti-malarial agents: therapeutic potential of artemisinins in neurodegeneration , 2019, Neural regeneration research.

[9]  H. Grabski,et al.  In vitro and in silico identification of the mechanism of interaction of antimalarial drug – artemisinin with human serum albumin and genomic DNA , 2019, bioRxiv.

[10]  S. Chi,et al.  Probing the interaction of a quercetin bioconjugate with Bcl‐2 in living human cancer cells with in‐cell NMR spectroscopy , 2018, FEBS letters.

[11]  Thomas Gaillard,et al.  Evaluation of AutoDock and AutoDock Vina on the CASF-2013 Benchmark , 2018, J. Chem. Inf. Model..

[12]  E. Bosch,et al.  Molecular interactions between warfarin and human (HSA) or bovine (BSA) serum albumin evaluated by isothermal titration calorimetry (ITC), fluorescence spectrometry (FS) and frontal analysis capillary electrophoresis (FA/CE). , 2018, Journal of pharmaceutical and biomedical analysis.

[13]  K. Zangger,et al.  Investigating Protein–Ligand Interactions by Solution Nuclear Magnetic Resonance Spectroscopy , 2018, Chemphyschem : a European journal of chemical physics and physical chemistry.

[14]  H. Matter,et al.  Identification and Characterization of a Single High-Affinity Fatty Acid Binding Site in Human Serum Albumin. , 2018, Angewandte Chemie.

[15]  Karunakaran A Kalesh,et al.  Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action , 2017, Medicinal research reviews.

[16]  David Cyranoski,et al.  Anti-parasite drugs sweep Nobel prize in medicine 2015 , 2015, Nature.

[17]  A. Ferreira,et al.  Human serum albumin-specific recognition of the natural herbal extract of Stryphnodendron polyphyllum through STD NMR, hyphenations and docking simulation studies , 2015 .

[18]  Zhengjun Cheng,et al.  Comparative studies on the interactions of dihydroartemisinin and artemisinin with bovine serum albumin using spectroscopic methods. , 2014, Luminescence : the journal of biological and chemical luminescence.

[19]  A. Ferreira,et al.  Crude to leads: a triple-pronged direct NMR approach in coordination with docking simulation. , 2013, The Analyst.

[20]  Hanlin Pu,et al.  Interaction of artemisinin and its derivatives with human serum albumin studied using spectroscopies and molecular modeling methods , 2013, Molecular Biology Reports.

[21]  J. Hamilton,et al.  Correspondence of fatty acid and drug binding sites on human serum albumin: a two-dimensional nuclear magnetic resonance study. , 2013, Biochemistry.

[22]  T. Carlomagno.  NMR in natural products: understanding conformation, configuration and receptor interactions. , 2012, Natural product reports.

[23]  Franklin L. Nobrega,et al.  Saturation-Transfer Difference (STD) NMR: A Simple and Fast Method for Ligand Screening and Characterization of Protein Binding , 2011 .

[24]  V. Barton,et al.  The Molecular Mechanism of Action of Artemisinin—The Debate Continues , 2010, Molecules.

[25]  Arthur J. Olson,et al.  AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading , 2009, J. Comput. Chem..

[26]  David S. Goodsell,et al.  AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility , 2009, J. Comput. Chem..

[27]  Peter Monecke,et al.  Crystallography-independent determination of ligand binding modes. , 2008, Angewandte Chemie.

[28]  Hong Liang,et al.  Study of the interaction of artemisinin with bovine serum albumin. , 2006, International journal of biological macromolecules.

[29]  P. Ascenzi,et al.  Allosteric modulation of drug binding to human serum albumin. , 2006, Mini reviews in medicinal chemistry.

[30]  S. Curry,et al.  Locating high-affinity fatty acid-binding sites on albumin by x-ray crystallography and NMR spectroscopy. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Enzo Terreno,et al.  The extraordinary ligand binding properties of human serum albumin , 2005, IUBMB life.

[32]  S. Curry,et al.  Structural basis of the drug-binding specificity of human serum albumin. , 2005, Journal of molecular biology.

[33]  Jens Meiler,et al.  The INPHARMA method: protein-mediated interligand NOEs for pharmacophore mapping. , 2005, Angewandte Chemie.

[34]  S. Curry,et al.  Crystal Structure Analysis of Warfarin Binding to Human Serum Albumin , 2001, The Journal of Biological Chemistry.

[35]  B. Meyer,et al.  Group epitope mapping by saturation transfer difference NMR to identify segments of a ligand in direct contact with a protein receptor. , 2001, Journal of the American Chemical Society.

[36]  S. Curry,et al.  Crystal structure analysis of warfarin binding to human serum albumin: anatomy of drug site I , 2001 .

[37]  S. Curry,et al.  Crystallographic analysis reveals common modes of binding of medium and long-chain fatty acids to human serum albumin. , 2000, Journal of molecular biology.

[38]  Pras,et al.  Isolation and identification of dihydroartemisinic acid hydroperoxide from artemisia annua: A novel biosynthetic precursor of artemisinin , 1999, Journal of natural products.

[39]  K. Kobayashi,et al.  Crystal structure of human serum albumin at 2.5 A resolution. , 1999, Protein engineering.

[40]  N. White,et al.  Assessment of the pharmacodynamic properties of antimalarial drugs in vivo , 1997, Antimicrobial agents and chemotherapy.

[41]  U. Kragh-Hansen,et al.  Evidence for a large and flexible region of human serum albumin possessing high affinity binding sites for salicylate, warfarin, and other ligands. , 1988, Molecular pharmacology.

[42]  U. Kragh-Hansen,et al.  Relations between high-affinity binding sites of markers for binding regions on human serum albumin. , 1985, The Biochemical journal.

[43]  F. G. Larsen,et al.  Interaction of warfarin with human serum albumin. A stoichiometric description. , 1985, Molecular pharmacology.

[44]  W. Müller,et al.  Characterization of an important drug binding area on human serum albumin including the high-affinity binding sites of warfarin and azapropazone. , 1982, Molecular pharmacology.

[45]  M. Otagiri,et al.  INTERACTION OF WARFARIN WITH HUMAN SERUM ALBUMIN , 1980 .