Antipsychotic clozapine binds catalase and preserves its activity in oxidative environment
Апстракт
Oxidative stress undoubtedly accompanies mental disorders, and
the pleiotropic effects of atypical antipsychotics, recommended
drugs in the treatment of psychosis, are not clarified at the
molecular level. Catalase is one of the key enzymes of the primary
antioxidant protection system. This work studied the binding
of second-generation antipsychotic drug Clozapine to
commercial bovine liver catalase. Using various spectroscopic
methods under simulated physiological conditions, we found
moderate binding affinity of clozapine for catalase (Ka ~ 2x105
M-1), the binding influenced the secondary and tertiary structure
of protein (according to UV-VIS and CD spectroscopy) and it
managed to slightly increase its thermal stability. In AAPH
induced oxidation experiments, we found that clozapine efficiently
protects catalase from free-radicals oxidation and preserves
its activity. Clozapine affects catalase activity in dose
dependant manner, having no significant effect at lower co...ncentrations
but significantly inhibiting enzyme at saturating concentrations.
In conclusion, our results indicate that the effect of
direct binding of clozapine to catalase can be both beneficial and
harmful and that this effect is dose dependent.
Кључне речи:
clozapine / catalase / activityИзвор:
FEBS Open Bio, 2022, 12, Supplement 1, 264-264Издавач:
- Wiley
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200168 (Универзитет у Београду, Хемијски факултет) (RS-MESTD-inst-2020-200168)
Напомена:
- The Biochemistry Global Summit, 25th IUBMB Congress, 46th FEBS Congress, 15th PABMB Congress, July 9-14, 2022, Lisbon, Portugal
Институција/група
IHTMTY - CONF AU - Vasović, Tamara AU - Gligorijević, Nikola AU - Minić, Simeon AU - Nikolić, Milan PY - 2022 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/6821 AB - Oxidative stress undoubtedly accompanies mental disorders, and the pleiotropic effects of atypical antipsychotics, recommended drugs in the treatment of psychosis, are not clarified at the molecular level. Catalase is one of the key enzymes of the primary antioxidant protection system. This work studied the binding of second-generation antipsychotic drug Clozapine to commercial bovine liver catalase. Using various spectroscopic methods under simulated physiological conditions, we found moderate binding affinity of clozapine for catalase (Ka ~ 2x105 M-1), the binding influenced the secondary and tertiary structure of protein (according to UV-VIS and CD spectroscopy) and it managed to slightly increase its thermal stability. In AAPH induced oxidation experiments, we found that clozapine efficiently protects catalase from free-radicals oxidation and preserves its activity. Clozapine affects catalase activity in dose dependant manner, having no significant effect at lower concentrations but significantly inhibiting enzyme at saturating concentrations. In conclusion, our results indicate that the effect of direct binding of clozapine to catalase can be both beneficial and harmful and that this effect is dose dependent. PB - Wiley C3 - FEBS Open Bio T1 - Antipsychotic clozapine binds catalase and preserves its activity in oxidative environment VL - 12 IS - Supplement 1 SP - 264 EP - 264 DO - 10.1002/2211-5463.13440 ER -
@conference{ author = "Vasović, Tamara and Gligorijević, Nikola and Minić, Simeon and Nikolić, Milan", year = "2022", abstract = "Oxidative stress undoubtedly accompanies mental disorders, and the pleiotropic effects of atypical antipsychotics, recommended drugs in the treatment of psychosis, are not clarified at the molecular level. Catalase is one of the key enzymes of the primary antioxidant protection system. This work studied the binding of second-generation antipsychotic drug Clozapine to commercial bovine liver catalase. Using various spectroscopic methods under simulated physiological conditions, we found moderate binding affinity of clozapine for catalase (Ka ~ 2x105 M-1), the binding influenced the secondary and tertiary structure of protein (according to UV-VIS and CD spectroscopy) and it managed to slightly increase its thermal stability. In AAPH induced oxidation experiments, we found that clozapine efficiently protects catalase from free-radicals oxidation and preserves its activity. Clozapine affects catalase activity in dose dependant manner, having no significant effect at lower concentrations but significantly inhibiting enzyme at saturating concentrations. In conclusion, our results indicate that the effect of direct binding of clozapine to catalase can be both beneficial and harmful and that this effect is dose dependent.", publisher = "Wiley", journal = "FEBS Open Bio", title = "Antipsychotic clozapine binds catalase and preserves its activity in oxidative environment", volume = "12", number = "Supplement 1", pages = "264-264", doi = "10.1002/2211-5463.13440" }
Vasović, T., Gligorijević, N., Minić, S.,& Nikolić, M.. (2022). Antipsychotic clozapine binds catalase and preserves its activity in oxidative environment. in FEBS Open Bio Wiley., 12(Supplement 1), 264-264. https://doi.org/10.1002/2211-5463.13440
Vasović T, Gligorijević N, Minić S, Nikolić M. Antipsychotic clozapine binds catalase and preserves its activity in oxidative environment. in FEBS Open Bio. 2022;12(Supplement 1):264-264. doi:10.1002/2211-5463.13440 .
Vasović, Tamara, Gligorijević, Nikola, Minić, Simeon, Nikolić, Milan, "Antipsychotic clozapine binds catalase and preserves its activity in oxidative environment" in FEBS Open Bio, 12, no. Supplement 1 (2022):264-264, https://doi.org/10.1002/2211-5463.13440 . .