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

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Protein-ligand interactions are crucial for understanding molecular mechanisms and structure-function relationships.
• Sulfonamide antibiotics are widely used, and their interactions with proteins like myoglobin are of significant interest.

Purpose of the Study:

• To investigate the binding characteristics of sulfonamide antibiotics (sulfamethazine and sulfadiazine) with myoglobin.
• To elucidate the molecular mechanism, structural changes, and energetic aspects of these drug-protein interactions.

Main Methods:

• Spectroscopic techniques (circular dichroism, fluorescence)
• Calorimetric methods (differential scanning calorimetry)
• Zeta potential analysis
• Computational methods (molecular docking)

Main Results:

• A 1:1 complex formed between myoglobin and both sulfonamide drugs with binding constants around 10^4 M^-1.
• Sulfamethazine exhibited higher binding affinity than sulfadiazine, attributed to its methyl substitutions.
• Drug binding induced loss of protein helicity, 3D structural perturbations, and protein destabilization.

Conclusions:

• The binding is primarily driven by non-polyelectrolytic forces, with a high probability of energy transfer between ligand and protein.
• Molecular docking identified potential binding sites within myoglobin pockets.
• The study provides insights into the structure-activity relationship of sulfonamide-myoglobin interactions.