Probing the Interactions of Ochratoxin B, Ochratoxin C, Patulin, Deoxynivalenol, and T-2 Toxin with Human Serum Albumin

Faisal, Zelma; Vörös, Virág; Fliszár-Nyúl, Eszter; Lemli, Beáta; Kunsági‐Máté, Sándor; Csepregi, Rita; Kőszegi, Tamás; Zsila, Ferenc; Poór, Miklós

doi:10.3390/toxins12060392

Cited by 17 publications

(10 citation statements)

References 62 publications

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“…The strong quenching effect of protamine on free insulin indicates easy accessibility of Tyr, resulting in a binding that is strongly dominated near the site close to Tyr residue in the protamine−insulin complex. 49 Additionally, a comparison of the fluorescence spectra of insulin under three different conditions is shown in Figure S8. The strength of the fluorescence intensity is in the following order: free insulin > Zn−insulin > Zn−insulin−protamine.…”

Section: Characterization Of Insulin Using Gelmentioning

confidence: 99%

Formation of Protamine and Zn–Insulin Assembly: Exploring Biophysical Consequences

et al. 2022

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The insulin−protamine interaction is at the core of the mode of action in many insulin formulations (Zn + insulin + protamine) and to treat diabetes, in which protamine is added to the stable form of hexameric insulin (Zn−insulin). However, due to the unavailability of quantitative data and a high-resolution structure, the binding mechanism of the insulin− protamine complex remains unknown. In this study, it was observed that Zn−insulin experiences destabilization as observed by the loss of secondary structure in circular dichroism (CD), and reduction in thermal stability in melting study, upon protamine binding. In isothermal titration calorimetry (ITC), it was found that the interactions were mostly enthalpically driven. This is in line with the positive ΔC m value (+880 cal mol −1 ), indicating the role of hydrophilic interactions in the complex formation, with the exposure of hydrophobic residues to the solvent, which was firmly supported by the 8-anilino-1-naphthalene sulfonate (ANS) binding study. The stoichiometry (N) value in ITC suggests the multiple insulin molecules binding to the protamine chain, which is consistent with the picture of the condensation of insulin in the presence of protamine. Atomic force microscopy (AFM) suggested the formation of a heterogeneous Zn−insulin−protamine complex. In fluorescence, Zn−insulin experiences strong Tyr quenching, suggesting that the location of the protamine-binding site is near Tyr, which is also supported by the molecular docking study. Since Tyr is critical in the stabilization of insulin self-assembly, its interaction with protamine may impair insulin's self-association ability and thermodynamic stability while at the same time promoting its flexible conformation desired for better biological activity.

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Section: Characterization Of Insulin Using Gelmentioning

confidence: 99%

Formation of Protamine and Zn–Insulin Assembly: Exploring Biophysical Consequences

et al. 2022

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“…Moreover, it is important to note that drugs can bind with different affinity to several pockets of the protein [ 4 , 5 ], and that there can exist competition for sites during the coadministration of drugs [ 3 , 6 , 7 ]. Even HSA pockets can be occupied by other undesirable exogenous compounds, such as some mycotoxins that could interfere with the drug transport [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Interactions between Human Serum Albumin (HSA) and Non-Steroidal Anti-Inflammatory (NSAIDs) Drugs by Multiwavelength Molecular Fluorescence, Structural and Computational Analysis

et al. 2021

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The interaction between drugs and transport proteins, such as albumins, is a key factor in drug bioavailability. One of the techniques commonly used for the evaluation of the drug-protein complex formation is fluorescence. This work studies the interaction of human serum albumin (HSA) with four non-steroidal anti-inflammatory drugs (NSAIDs)—ibuprofen, flurbiprofen, naproxen, and diflunisal—by monitoring the fluorescence quenching when the drug-albumin complex is formed. Two approaches—the double logarithm Stern-Volmer equation and the STAR program—are used to evaluate the binding parameters. The results are analyzed considering the binding properties, determined by using other complementary techniques and the available structural information of albumin complexes with NSAID-related compounds. Finally, this combined analysis has been synergistically used to interpret the binding of flurbiprofen to HSA.

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“…Based on Equation (3), the log K a values were also calculated, showing similar data to that determined in quenching studies and also suggesting that the stability of the CPA–HSA complex is approximately 2.5-fold higher compared to that of STC–HSA ( Table 1 ). Thus, both spectroscopic and ultracentrifugation experiments demonstrated the relevant, moderately strong interactions of CPA and STC with the protein, similar to that of aflatoxins (log K a = 4.3 to 4.6) [ 40 ], patulin (log K a = 4.1) [ 20 ], or phenytoin (log K a = 4.0) [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

“…The major binding sites of drugs and xenobiotics are Sudlow’s site I (subdomain IIA), Sudlow’s site II (subdomain IIIA), and Heme site (or FA1; subdomain IB) on HSA [ 16 , 18 ]. Strong interactions of certain mycotoxins with HSA have been reported, including ochratoxins ( K a ≈ 10 6 to 10 7 L/mol) [ 19 , 20 ], alternariol ( K a = 4 × 10 5 L/mol) [ 21 ], citrinin ( K a = 2 × 10 5 L/mol) [ 22 ], and zearalenone ( K a = 10 5 L/mol) [ 23 ]. However, we did not find data in regard to the albumin binding of BEA, CPA, or STC in the scientific literature.…”

Section: Introductionmentioning

confidence: 99%

Interaction of the Emerging Mycotoxins Beauvericin, Cyclopiazonic Acid, and Sterigmatocystin with Human Serum Albumin

et al. 2022

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Beauvericin (BEA), cyclopiazonic acid (CPA), and sterigmatocystin (STC) are emerging mycotoxins. They appear as contaminants in food and animal feed, leading to economic losses and health risks. Human serum albumin (HSA) forms stable complexes with certain mycotoxins, including ochratoxins, alternariol, citrinin, and zearalenone. HSA binding can influence the toxicokinetics of xenobiotics, and albumin can also be considered and applied as a relatively cheap affinity protein. Therefore, we examined the potential interactions of BEA, CPA, and STC with HSA employing fluorescence spectroscopy, ultracentrifugation, ultrafiltration, and molecular modeling. Spectroscopic and ultracentrifugation studies demonstrated the formation of low-affinity BEA–HSA (Ka ≈ 103 L/mol) and moderately strong CPA–HSA and STC–HSA complexes (Ka ≈ 104 L/mol). In ultrafiltration experiments, CPA slightly displaced each site marker (warfarin, naproxen, and camptothecin) tested, while BEA and STC did not affect significantly the albumin binding of these drugs. Modeling studies suggest that CPA occupies Sudlow’s site I, while STC binds to the Heme site (FA1) on HSA. Considering the interactions of CPA with the site markers, the CPA–HSA interaction may have toxicological importance.

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Probing the Interactions of Ochratoxin B, Ochratoxin C, Patulin, Deoxynivalenol, and T-2 Toxin with Human Serum Albumin

Cited by 17 publications

References 62 publications

Formation of Protamine and Zn–Insulin Assembly: Exploring Biophysical Consequences

Formation of Protamine and Zn–Insulin Assembly: Exploring Biophysical Consequences

Evaluation of the Interactions between Human Serum Albumin (HSA) and Non-Steroidal Anti-Inflammatory (NSAIDs) Drugs by Multiwavelength Molecular Fluorescence, Structural and Computational Analysis

Interaction of the Emerging Mycotoxins Beauvericin, Cyclopiazonic Acid, and Sterigmatocystin with Human Serum Albumin

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