Characterization of Climbazole-Bovine serum albumin interaction by experimental and in silico approaches

Kabir M. Z., Tayyab H., Erkmen C., KURBANOĞLU S., Mohamad S. B., USLU B.

SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY, cilt.288, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 288
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1016/j.saa.2022.122197
  • Dergi Adı: SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, Compendex, EMBASE, INSPEC, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Bovine serum albumin, Climbazole, Fluorescence quenching, Molecular dynamics simulation, Drug-protein interaction, MOLECULAR DOCKING, ENZYMATIC-PROPERTIES, PRACTICAL ASPECTS, PROTEIN-BINDING, LIGAND-BINDING, FORCE-FIELD, FLUORESCENCE, THERMODYNAMICS, SPECTROSCOPY, STABILITY
  • Ankara Üniversitesi Adresli: Evet

Özet

Interactive association of an antifungal drug, climbazole (CBZ) with the carrier protein in bovine circulation, bovine serum albumin (BSA) was explored by fluorescence and absorption spectroscopy along with in silico techniques. The fluorescence and absorption spectral alterations of the protein upon addition of CBZ affirmed the complex foration between CBZ and BSA. The inverse temperature dependence behaviour of the KSVvalues as well as the hyperchromic result of the protein's absorption signals characterized CBZ-triggered quenching of BSA fluorescence as the static quenching. A weak binding affinity (Ka = 3.12-1.90-x 103 M-1) was reported towards the CBZ-BSA association process. Interpretation of thermodynamic data (entropy change = +14.68 J mol- 1 K-1 and enthalpy change = -15.07 kJ mol-1) and in silico analyses anticipated that hydrophobic forces, van der Waals forces and hydrogen bonds were the key intermolecular forces in the complex stabilization. Inclusion of CBZ to BSA produced microenvironmental perturbations around Tyr and Trp residues, and also significantly defended temperature-induced destabilization of BSA. The binding locus of CBZ was detected in the proximity of Sudlow's sites I (subdomain IIA) and II (subdomain IIIA) of BSA, exhibiting greater preference towards site II, as revealed by competitive site-marker displacement investigations and in silico analysis. The stability of the CBZ-BSA complex was further validated by the molecular dynamics simulation assessments.