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
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.
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%),…
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Taxonomy
TopicsPharmacogenetics and Drug Metabolism · Malaria Research and Control · Photodynamic Therapy Research Studies