Structural Impact of 4‐Hydroxynonenal Modification on Human Cytochrome CYP4F11

Olena Gnatyuk; Oleksii Skorokhod; Alessandro Damin; Mykhailo Chaika; Fateme Naeimaeirouhani; Loris Pica; Anita Tomatis; Aleksandra Smorygo; Taras Voitsitskyi; Gianluca Catucci; Galyna Dovbeshko; Gianfranco Gilardi

doi:10.1002/cmdc.202500935

journal article Open Access Jan 01, 2026

Structural Impact of 4‐Hydroxynonenal Modification on Human Cytochrome CYP4F11

Olena Gnatyuk Oleksii Skorokhod

Alessandro Damin Mykhailo Chaika

Fateme Naeimaeirouhani Loris Pica Anita Tomatis Aleksandra Smorygo Taras Voitsitskyi

Gianluca Catucci Galyna Dovbeshko Gianfranco Gilardi

ChemMedChem Vol. 21 No. 2 · Wiley

View at Publisher Save 10.1002/cmdc.202500935

Abstract

Posttranslational modifications of human enzymes play a crucial role in disease development. 4‐hydroxynonenal (4‐HNE), a lipid peroxidation product, can modify proteins and disrupt their function. Human cytochrome CYP4F11, involved in lipid metabolism and xenobiotic degradation, was previously shown to be inhibited by 4‐HNE in a malaria model, where hemozoin‐induced 4‐HNE formation occurs in monocytes. However, structural changes to CYP4F11 upon 4‐HNE modification had not been described. In this study, we investigated these changes using differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and Raman spectroscopy. DSC thermograms revealed an increased energetic barrier to unfolding, suggesting structural reorganization. FTIR data, supported by computational analysis, showed a decrease in alpha‐helix content (0.2–2.5%) and an increase in beta‐structure (2.2–3.3%), along with altered disordered regions. Raman spectroscopy indicated significant changes in luminescence decay across emission wavelengths. These structural alterations induced by 4‐HNE conjugation (protein lipoxidation) may significantly influence the enzymatic activity of CYP4F11, with potential implications for lipid metabolism and xenobiotic detoxification.

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Published: Jan 01, 2026
Vol/Issue: 21(2)
License: View

Authors

O

Olena Gnatyuk

Institute of Physics National Academy of Sciences of Ukraine Kyiv Ukraine

O

Oleksii Skorokhod

Department of Life Sciences and Systems Biology University of Torino Torino Italy

A

Alessandro Damin

Department of Chemistry University of Torino Torino Italy

M

Mykhailo Chaika

Institute of Low Temperatures and Structural Research PAN Wroclaw Poland

F

Fateme Naeimaeirouhani

Department of Life Sciences and Systems Biology University of Torino Torino Italy

L

Loris Pica

Department of Life Sciences and Systems Biology University of Torino Torino Italy

A

Anita Tomatis

Department of Life Sciences and Systems Biology University of Torino Torino Italy

A

Aleksandra Smorygo

Department of Life Sciences and Systems Biology University of Torino Torino Italy

T

Taras Voitsitskyi

Institute of Physics National Academy of Sciences of Ukraine Kyiv Ukraine; Receptor.AI Inc. London UK

G

Gianluca Catucci

Department of Life Sciences and Systems Biology University of Torino Torino Italy

G

Galyna Dovbeshko

Institute of Physics National Academy of Sciences of Ukraine Kyiv Ukraine; Department of Life Sciences and Systems Biology University of Torino Torino Italy

G

Gianfranco Gilardi

Department of Life Sciences and Systems Biology University of Torino Torino Italy

Cite This Article

Olena Gnatyuk, Oleksii Skorokhod, Alessandro Damin, et al. (2026). Structural Impact of 4‐Hydroxynonenal Modification on Human Cytochrome CYP4F11. ChemMedChem, 21(2). https://doi.org/10.1002/cmdc.202500935

Structural Impact of 4‐Hydroxynonenal Modification on Human Cytochrome CYP4F11

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