# Structural Impact of 4‐Hydroxynonenal Modification on Human Cytochrome CYP4F11

## TL;DR

This study shows how 4-HNE, a harmful molecule from lipid breakdown, changes the structure of the human enzyme CYP4F11, which could affect its function in lipid metabolism and detoxification.

## Contribution

The study is the first to describe structural changes in CYP4F11 caused by 4-HNE modification using DSC, FTIR, and Raman spectroscopy.

## Key findings

- 4-HNE modification increases the energetic barrier to unfolding in CYP4F11.
- There is a decrease in alpha-helix content and an increase in beta-structure in modified CYP4F11.
- Raman spectroscopy shows significant luminescence decay changes in modified CYP4F11.

## 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.

Protein lipoxidation by 4‐hydroxynonenal induces conformational and stability changes in human CYP4F11, as revealed by DSC, FTIR, and Raman spectroscopy, with potential consequences for enzymatic function.© 2026 WILEY‐VCH GmbH