title: Supramolecular interaction of 6-shogaol, a therapeutic agent of Zingiber officinale with human serum albumin as elucidated by spectroscopic, calorimetric and molecular docking methods.
abstract: BACKGROUND
  6-Shogaol, one of the main bioactive constituents of Zingiber officinale has been shown to possess various therapeutic properties. Interaction of a therapeutic compound with plasma proteins greatly affects its pharmacokinetic and pharmacodynamic properties.
  
  
  OBJECTIVE
  The present investigation was undertaken to characterize the interaction between 6-shogaol and the main in vivo transporter, human serum albumin (HSA).
  
  
  METHODS
  Various binding characteristics of 6-shogaol-HSA interaction were studied using fluorescence spectroscopy. Thermal stability of 6-shogaol-HSA system was determined by circular dichroism (CD) and differential scanning calorimetric (DSC) techniques. Identification of the 6-shogaol binding site on HSA was made by competitive drug displacement and molecular docking experiments.
  
  
  RESULTS
  Fluorescence quench titration results revealed the association constant, Ka of 6-shogaol-HSA interaction as 6.29 ± 0.33 × 10(4) M(-1) at 25 ºC. Values of the enthalpy change (-11.76 kJ mol(-1)) and the entropy change (52.52 J mol(-1) K(-1)), obtained for the binding reaction suggested involvement of hydrophobic and van der Waals forces along with hydrogen bonds in the complex formation. Higher thermal stability of HSA was noticed in the presence of 6-shogaol, as revealed by DSC and thermal denaturation profiles. Competitive ligand displacement experiments along with molecular docking results suggested the binding preference of 6-shogaol for Sudlow's site I of HSA.
  
  
  CONCLUSIONS
  All these results suggest that 6-shogaol binds to Sudlow's site I of HSA through moderate binding affinity and involves hydrophobic and van der Waals forces along with hydrogen bonds.
authors.affiliation: Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: shevrzl@gmail.com.
authors.forename: S R
authors.initials: SR
authors.lastname: Feroz
authors.affiliation: Bioinformatics Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia; Centre of Research for Computational Sciences and Informatics for Biology, Bioindustry, Environment, Agriculture and Healthcare (CRYSTAL), Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: S B
authors.initials: SB
authors.lastname: Mohamad
authors.affiliation: Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: G S
authors.initials: GS
authors.lastname: Lee
authors.affiliation: Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: S N A
authors.initials: SN
authors.lastname: Malek
authors.affiliation: Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia; Centre of Research for Computational Sciences and Informatics for Biology, Bioindustry, Environment, Agriculture and Healthcare (CRYSTAL), Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: saadtayyab2004@yahoo.com.
authors.forename: S
authors.initials: S
authors.lastname: Tayyab
mesh_terms: D001665:Binding Sites; D002152:Calorimetry, Differential Scanning; D002396:Catechols / Q000737:chemistry*; D002942:Circular Dichroism; D020939:Zingiber officinale / Q000737:chemistry*; D006358:Hot Temperature; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D012709:Serum Albumin / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: D002396:Catechols; D012709:Serum Albumin; C040115:shogaol
keywords: 6-Shogaol; Differential scanning calorimetry; Human serum albumin; Ligand–protein interaction; Molecular docking; Zingiber officinale