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On the Biophysical Investigation of Sulfamethazine‐Hemoglobin Binding and the Resulting Adverse Effects of Antibiotics
Author(s) -
Ovung Aben,
Mavani A.,
Chatterjee Sabyasachi,
Das Abhi,
Suresh Kumar Gopinatha,
Bhuiya Sutanwi,
Das Suman,
Bhattacharyya Jhimli
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202003256
Subject(s) - isothermal titration calorimetry , chemistry , hydrogen bond , circular dichroism , binding constant , binding site , methemoglobin , titration , fluorescence spectroscopy , crystallography , hemoglobin , fluorescence , molecule , organic chemistry , biochemistry , physics , quantum mechanics
Abstract Binding of the well‐known antibiotic drug sulfamethazine (SMZ) with tetrameric heme protein, hemoglobin (Hb), was studied using spectroscopic, calorimetric and molecular docking techniques. SMZ belongs to the sulfonamide group of medicines with versatile applications. Nevertheless, it can be biologically harmful if used in excess or in an uncontrolled manner. The binding induced absorbance and fluorescence data indicated a ground state complex formation between the drug and the protein with 1 : 1 stoichiometry. Drug induced conformational perturbation of Hb structure was investigated with circular dichroism and synchronous fluorescence. The binding constant obtained from spectroscopy was in the order of 10 4 M −1 which was further confirmed by isothermal titration calorimetry. This may be higher compared to that of the oxygenation in Hb; thus SMZ binding can subsequently interrupt the oxygen transporting property of this iron protein. FRET analysis showed that the distance between SMZ and Hb is ∼3.75 nm, which is suitable for an effective binding. The MD simulation substantiated the mode and site of binding by confirming the factors contributing to the binding energy. It shows that SMZ binds to the central cavity close to subunit α 1 ‐helix of Hb. Residues around the drug forms hydrogen bonding and increases hydrophobicity to stabilize the SMZ−Hb complex. The binding interaction appears to be dominated by H‐bond formation and electrostatic and hydrophobic forces. This is in agreement with the thermodynamic analyses and contributes to the binding energy.