ArticleBiochemistry2021
Structural Dynamics of Cytochrome P450 3A4 in the Presence of Substrates and Cytochrome P450 Reductase.
Article in Biochemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Elucidating the Oxygen-Activation Mechanism in Nonheme MnInorganic chemistry · 2026Article
- Structural context of NADPH-cytochrome P450 reductase mutations that alter cytochrome P450 1A2 substrate regioselectivity.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Mass spectrometry footprinting reveals microsomal CYP2A6 structural changes induced by interaction with its reductase flavin mononucleotide domain.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Impact of metabolic enzyme activity variability on dabrafenib disposition.Frontiers in pharmacology · 2025Article
- A Structural Comparison of Oral SARS-CoV-2 Drug Candidate Ibuzatrelvir Complexed with the Main Protease (MJACS Au · 2024Article
- Charged Amino Acids in the Transmembrane Helix Strongly Affect the Enzyme Activity of Aromatase.International journal of molecular sciences · 2024Article
- Allosteric modulation of cytochrome P450 enzymes by the NADPH cytochrome P450 reductase FMN-containing domain.The Journal of biological chemistry · 2023Article
- Nanodisc-embedded cytochrome P450 P3A4 binds diverse ligands by distributing conformational dynamics to its flexible elements.Journal of inorganic biochemistry · 2023Article
- Binding of cytochrome P450 27C1, a retinoid desaturase, to its accessory protein adrenodoxin.Archives of biochemistry and biophysics · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Cytochrome P450 3A4 (CYP3A4) is the most important drug-metabolizing enzyme in humans and has been associated with harmful drug interactions. The activity of CYP3A4 is known to be modulated by several compounds and by the electron transfer partner, cytochrome P450 reductase (CPR). The underlying mechanism of these effects, however, is poorly understood. We have used hydrogen-deuterium exchange mass spectrometry to investigate the impact of binding of CPR and of three different substrates (7-benzyloxy-4-trifluoromethyl-coumarin, testosterone, and progesterone) on the conformational dynamics of CYP3A4. Here, we report that interaction of CYP3A4 with substrates or with the oxidized or reduced forms of CPR leads to a global rigidification of the CYP3A4 structure. This was evident from the suppression of deuterium exchange in several regions of CYP3A4, including regions known to be involved in protein-protein interactions (helix C) and substrate binding and specificity (helices B' and E, and loop K/β1). Furthermore, the bimodal isotopic distributions observed for some CYP3A4-derived peptides were drastically impacted upon binding to CPR and/or substrates, suggesting the existence of stable CYP3A4 conformational populations that are perturbed by ligand/CPR binding. The results have implications for understanding the mechanisms of ligand binding, allostery, and catalysis in CYP enzymes.
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