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Article

Catalase Specifically Binds Antipsychotic Clozapine: Experimental and In Silico Insights into Interactions, Complex Stability, and Dose-Dependent Enzyme Activity Modulation

by
Tamara Vasović
1,
Milica Radibratović
2,
Dušan Spasić
3,
Simeon Minić
1,
Čedo Miljević
4,
Nikola Gligorijević
2,* and
Milan Nikolić
1,*
1
Department of Biochemistry, Faculty of Chemistry, University of Belgrade, 11000 Belgrade, Serbia
2
Department of Chemistry, Institute for Chemistry, Technology and Metallurgy, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia
3
Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
4
Institute of Mental Health, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
*
Authors to whom correspondence should be addressed.
Molecules 2026, 31(8), 1294; https://doi.org/10.3390/molecules31081294
Submission received: 25 February 2026 / Revised: 30 March 2026 / Accepted: 11 April 2026 / Published: 16 April 2026
(This article belongs to the Special Issue Protein–Ligand Interactions, 2nd Edition)
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Abstract

Oxidative stress is intrinsically linked to mental disorders, involving an imbalance between reactive species and antioxidant defenses, where catalase is an essential, ubiquitous antioxidant enzyme. The pleiotropic effects of antipsychotic drugs, used for schizophrenia and mood disorders, are not fully elucidated at the molecular level. This study characterized the binding of a highly effective but potentially dangerous antipsychotic, clozapine (CLZ), to commercial bovine liver catalase (BLC). Using various spectroscopic methods under simulated physiological conditions, we found a moderate binding affinity of CLZ for BLC (Ka = 1.4 × 10−5 M−1), subtly influencing the protein’s secondary and tertiary structures and slightly increasing its thermal stability. CLZ efficiently protected BLC against free-radical-induced oxidation and preserved its catalytic activity for decomposing toxic hydrogen peroxide. The effect of CLZ on BLC antioxidant activity was dual: no significant effect at lower, physiologically relevant concentrations, but significant inhibition at saturating, toxic drug concentrations. Molecular docking and molecular dynamics results indicated the presence of two specific binding sites within BLC monomers, one located near its active site. In conclusion, our in vitro results indicate that CLZ’s specific binding to BLC can be both beneficial and potentially harmful, and that this effect is dose-dependent.
Keywords: clozapine; catalase; binding interactions; enzyme structure; enzyme activity clozapine; catalase; binding interactions; enzyme structure; enzyme activity

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MDPI and ACS Style

Vasović, T.; Radibratović, M.; Spasić, D.; Minić, S.; Miljević, Č.; Gligorijević, N.; Nikolić, M. Catalase Specifically Binds Antipsychotic Clozapine: Experimental and In Silico Insights into Interactions, Complex Stability, and Dose-Dependent Enzyme Activity Modulation. Molecules 2026, 31, 1294. https://doi.org/10.3390/molecules31081294

AMA Style

Vasović T, Radibratović M, Spasić D, Minić S, Miljević Č, Gligorijević N, Nikolić M. Catalase Specifically Binds Antipsychotic Clozapine: Experimental and In Silico Insights into Interactions, Complex Stability, and Dose-Dependent Enzyme Activity Modulation. Molecules. 2026; 31(8):1294. https://doi.org/10.3390/molecules31081294

Chicago/Turabian Style

Vasović, Tamara, Milica Radibratović, Dušan Spasić, Simeon Minić, Čedo Miljević, Nikola Gligorijević, and Milan Nikolić. 2026. "Catalase Specifically Binds Antipsychotic Clozapine: Experimental and In Silico Insights into Interactions, Complex Stability, and Dose-Dependent Enzyme Activity Modulation" Molecules 31, no. 8: 1294. https://doi.org/10.3390/molecules31081294

APA Style

Vasović, T., Radibratović, M., Spasić, D., Minić, S., Miljević, Č., Gligorijević, N., & Nikolić, M. (2026). Catalase Specifically Binds Antipsychotic Clozapine: Experimental and In Silico Insights into Interactions, Complex Stability, and Dose-Dependent Enzyme Activity Modulation. Molecules, 31(8), 1294. https://doi.org/10.3390/molecules31081294

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