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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.

SUBMITTER: Ovung A

PROVIDER: S-EPMC8851458 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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

Ovung Aben A Mavani A A Ghosh Ambarnil A Chatterjee Sabyasachi S Das Abhi A Suresh Kumar Gopinatha G Ray Debes D Aswal Vinod K VK Bhattacharyya Jhimli J

ACS omega 20220204 6

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 observe ...[more]

PMID: 35187312

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Project description:Calorimetric and fluorescence techniques were used to characterize the binding of aminoglycosides-neomycin, paromomycin, and ribostamycin, with 5'-dA(12)-x-dT(12)-x-dT(12)-3' intramolecular DNA triplex (x = hexaethylene glycol) and poly(dA).2poly(dT) triplex. Our results demonstrate the following features: (1) UV thermal analysis reveals that the T(m) for triplex decreases with increasing pH value in the presence of neomycin, while the T(m) for the duplex remains unchanged. (2) The binding affinity of neomycin decreases with increased pH, although there is an increase in observed binding enthalpy. (3) ITC studies conducted in two buffers (sodium cacodylate and MOPS) yield the number of protonated drug amino groups (Deltan) as 0.29 and 0.40 for neomycin and paromomycin interaction with 5'-dA(12)-x-dT(12)-x-dT(12)-3', respectively. (4) The specific heat capacity change (DeltaC(p)) determined by ITC studies is negative, with more negative values at lower salt concentrations. From 100 mM to 250 mM KCl, the DeltaC(p) ranges from -402 to -60 cal/(mol K) for neomycin. At pH 5.5, a more positive DeltaC(p) is observed, with a value of -98 cal/(mol K) at 100 mM KCl. DeltaC(p) is not significantly affected by ionic strength. (5) Salt dependence studies reveal that there are at least three amino groups of neomycin participating in the electrostatic interactions with the triplex. (6) FID studies using thiazole orange were used to derive the AC(50) (aminoglycoside concentration needed to displace 50% of the dye from the triplex) values. Neomycin shows a seven fold higher affinity than paromomycin and eleven fold higher affinity than ribostamycin at pH 6.8. (7) Modeling studies, consistent with UV and ITC results, show the importance of an additional positive charge in triplex recognition by neomycin. The modeling and thermodynamic studies indicate that neomycin binding to the DNA triplex depends upon significant contributions from charge as well as shape complementarity of the drug to the DNA triplex Watson-Hoogsteen groove.

Dataset Information

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

Publications

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

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