Heme Protein Binding of Sulfonamide Compounds: A Correlation Study by Spectroscopic, Calorimetric, and Computational Methods

Abstract

Protein–ligand interaction studies are useful to determine the molecular mechanism of the binding phenomenon, leading to the establishment of the structure–function relationship. Here, we report the binding of well-known antibiotic sulfonamide drugs (sulfamethazine, SMZ; and sulfadiazine, SDZ) with heme protein myoglobin (Mb) using spectroscopic, calorimetric, ζ potential, and computational methods. Formation of a 1:1 complex between the ligand and Mb through well-defined equilibrium was observed. The binding constants obtained between Mb and SMZ/SDZ drugs were on the order of 104 M–1. SMZ with two additional methyl (−CH3) substitutions has higher affinity than SDZ. Upon drug binding, a notable loss in the helicity (via circular dichroism) and perturbation of the three-dimensional (3D) protein structure (via infrared and synchronous fluorescence experiments) were observed. The binding also indicated the dominance of non-polyelectrolytic forces between the amino acid residues of the protein and the drugs. The ligand–protein binding distance signified high probability of energy transfer between them. Destabilization of the protein structure upon binding was evident from differential scanning calorimetry results and ζ potential analyses. Molecular docking presented the best probable binding sites of the drugs inside protein pockets. Thus, the present study explores the potential binding characteristics of two sulfonamide drugs (with different substitutions) with myoglobin, correlating the structural and energetic aspects.

A Novel Biomaterial for Decolorization of Azo Dyes: Myoglobin‐Zn(II) Assisted Hybrid Nanoflowers

“…The band at ∼3346 cm −1 in the spectrum of free myoglobin was represented another characteristic protein band that indicates the presence of ‐CH 2 and ‐NH. The FT‐IR spectra results are quite similar to the FT‐IR spectra represented by Miao and Ovung [62,63] . In the spectrum of MbNFs@Zn, the peak in the range ∼2800–3600 cm −1 was indicated the existence of ‐CH 2 , ‐CH 3 and ‐NH groups.…”

“…The FT-IR spectra results are quite similar to the FT-IR spectra represented by Miao and Ovung. [62,63] In the spectrum of MbNFs@Zn, the peak in the range ~2800-3600 cm À 1 was indicated the existence of -CH 2 , -CH 3 and -NH groups. The peak at ~1634 cm À 1 was attributed to -C=O stretching in the nanoflowers structure.…”

Protein‐binding characteristics of yohimbine, a natural indole alkaloid‐based drug for erectile dysfunction

“…If Δ H < 0, Δ S < 0 then van der Waals and hydrogen bonds are considered to be the significant force. [ 35,36 ] The thermodynamic parameters Δ G° (Gibbs free energy change), Δ H° (enthalpy change) and Δ S° (entropy change) [ 37 ] of Yoh and Hb were studied by analyzing the result obtained from temperature‐dependent fluorescence spectroscopy and a detailed preview into the interaction of forces involved in the system was obtained by applying the van 't Hoff analysis [ 38,39 ] (Figure 4): where R is the gas constant (R = 8.314 × 10 −3 kJ/mol K), T is the temperature (288.15, 293.15, 298.15, 303.15, and 308.15 K), and K a is the binding constant at each temperature. [ 39 ] The van 't Hoff plots were in relatively straight lines after plotting ln K versus 1/T.…”

“…Therefore, it can be noted that nonpolyelectrolytic forces (namely van der Waals interactions, π–π stacking, H bonding and hydrophobic transfer) act in an assertive role to stabilize the drug and protein complex. [ 36,46,47 ]…”

“…If ΔH < 0, ΔS < 0 then van der Waals and hydrogen bonds are considered to be the significant force. [35,36] The thermodynamic parameters ΔG (Gibbs free energy change), ΔH (enthalpy change) and ΔS (entropy change) [37] of Yoh and Hb were studied by analyzing the result obtained from temperature-dependent fluorescence spectroscopy and a detailed preview into the interaction of forces involved in the system was obtained by applying the van 't Hoff analysis [38,39] (Figure 4):…”