ArticleThe Journal of biological chemistry2016
Mutants of Cytochrome P450 Reductase Lacking Either Gly-141 or Gly-143 Destabilize Its FMN Semiquinone.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- 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
- Cryo-EM reveals an ensemble of cytochrome P450 reductase conformations in solution.Protein science : a publication of the Protein Society · 2026Article
- Recent Advances in Elucidating the Mechanism of the NADPH-Cytochrome P450 Reductase-Mediated Electron Transfer Cycle: Experimental and Computational Perspectives.Molecules (Basel, Switzerland) · 2025Review
- A flexible linker of 8-amino acids between the membrane binding segment and the FMN domain of cytochrome P450 reductase is necessary for optimal activity.Journal of inorganic biochemistry · 2024Article
- Exploring Novel Variants of the Cytochrome P450 Reductase Gene (Biomolecules · 2023Article
- Roles of Ferredoxin-NADPAntioxidants (Basel, Switzerland) · 2022Review
- Loss of Protein Stability and Function Caused by P228L Variation in NADPH-Cytochrome P450 Reductase Linked to Lower Testosterone Levels.International journal of molecular sciences · 2022Article
- Integration of transcriptomic and metabolomic analysis of the mechanism of dietaryFrontiers in veterinary science · 2022Article
- Article
- The FMN "140s Loop" of Cytochrome P450 Reductase Controls Electron Transfer to Cytochrome P450.International journal of molecular sciences · 2021Article
- Conformational Landscape of Cytochrome P450 Reductase Interactions.International journal of molecular sciences · 2021Article
- The Role of the FMN-Domain of Human Cytochrome P450 Oxidoreductase in Its Promiscuous Interactions With Structurally Diverse Redox Partners.Frontiers in pharmacology · 2020Article
- Short-lived neutral FMN and FAD semiquinones are transient intermediates in cryo-reduced yeast NADPH-cytochrome P450 reductase.Archives of biochemistry and biophysics · 2019Article
- A Minimal Functional Complex of Cytochrome P450 and FBD of Cytochrome P450 Reductase in Nanodiscs.Angewandte Chemie (International ed. in English) · 2018Article
- Article
- Application of methyl-TROSY to a large paramagnetic membrane protein without perdeuteration:Journal of biomolecular NMR · 2018Article
- Orchestrated Domain Movement in Catalysis by Cytochrome P450 Reductase.Scientific reports · 2017Article
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7 authors.
Funding
Abstract
NADPH-cytochrome P450 oxidoreductase transfers electrons from NADPH to cytochromes P450 via its FAD and FMN. To understand the biochemical and structural basis of electron transfer from FMN-hydroquinone to its partners, three deletion mutants in a conserved loop near the FMN were characterized. Comparison of oxidized and reduced wild type and mutant structures reveals that the basis for the air stability of the neutral blue semiquinone is protonation of the flavin N5 and strong H-bond formation with the Gly-141 carbonyl. The ΔGly-143 protein had moderately decreased activity with cytochrome P450 and cytochrome c It formed a flexible loop, which transiently interacts with the flavin N5, resulting in the generation of both an unstable neutral blue semiquinone and hydroquinone. The ΔGly-141 and ΔG141/E142N mutants were inactive with cytochrome P450 but fully active in reducing cytochrome c In the ΔGly-141 mutants, the backbone amide of Glu/Asn-142 forms an H-bond to the N5 of the oxidized flavin, which leads to formation of an unstable red anionic semiquinone with a more negative potential than the hydroquinone. The semiquinone of ΔG141/E142N was slightly more stable than that of ΔGly-141, consistent with its crystallographically demonstrated more rigid loop. Nonetheless, both ΔGly-141 red semiquinones were less stable than those of the corresponding loop in cytochrome P450 BM3 and the neuronal NOS mutant (ΔGly-810). Our results indicate that the catalytic activity of cytochrome P450 oxidoreductase is a function of the length, sequence, and flexibility of the 140s loop and illustrate the sophisticated variety of biochemical mechanisms employed in fine-tuning its redox properties and function.
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