ArticleBiochemistry2011
Uncovering the role of hydrophobic residues in cytochrome P450-cytochrome P450 reductase interactions.
Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 45 citations in OpenAlex.
- The role of CYP3A-CYP2E1 interactions in activation of CYP3A enzymes by chronic alcohol exposure.bioRxiv : the preprint server for biology · 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
- InteracTor: Feature engineering and explainable AI for profiling protein structure-interaction-function relationships.PLoS computational biology · 2025Article
- 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
- Article
- 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
- Structure-based virtual screening of CYP1A1 inhibitors: towards rapid tier-one assessment of potential developmental toxicants.Archives of toxicology · 2021Article
- An electron transfer competent structural ensemble of membrane-bound cytochrome P450 1A1 and cytochrome P450 oxidoreductase.Communications biology · 2021Article
- Clinical outcomes and characteristics of P30L mutations in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.Endocrine · 2020Review
- Probing membrane enhanced protein-protein interactions in a minimal redox complex of cytochrome-P450 and P450-reductase.Chemical communications (Cambridge, England) · 2019Article
- Effect of Gambogenic Acid on Cytochrome P450 1A2, 2B1 and 2E1, and Constitutive Androstane Receptor in Rats.European journal of drug metabolism and pharmacokinetics · 2018Article
- Cytochrome P450 17A1 Interactions with the FMN Domain of Its Reductase as Characterized by NMR.The Journal of biological chemistry · 2016Article
- Protein/protein interactions in the mammalian heme degradation pathway: heme oxygenase-2, cytochrome P450 reductase, and biliverdin reductase.The Journal of biological chemistry · 2014Article
- Role of protein-protein interactions in cytochrome P450-mediated drug metabolism and toxicity.Chemical research in toxicology · 2014Review
- Structure and function of cytochrome P450S in insect adaptation to natural and synthetic toxins: insights gained from molecular modeling.Journal of chemical ecology · 2013Review
- Structure-phenotype correlations of human CYP21A2 mutations in congenital adrenal hyperplasia.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Interactions between CYP2E1 and CYP2B4: effects on affinity for NADPH-cytochrome P450 reductase and substrate metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Reaction of human cytochrome P450 3A4 with peroxynitrite: nitrotyrosine formation on the proximal side impairs its interaction with NADPH-cytochrome P450 reductase.Chemical research in toxicology · 2012Article
- NADPH-cytochrome P450 oxidoreductase: prototypic member of the diflavin reductase family.Archives of biochemistry and biophysics · 2012Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Cytochrome P450 (CYP or P450)-mediated drug metabolism requires the interaction of P450s with their redox partner, cytochrome P450 reductase (CPR). In this work, we have investigated the role of P450 hydrophobic residues in complex formation with CPR and uncovered novel roles for the surface-exposed residues V267 and L270 of CYP2B4 in mediating CYP2B4--CPR interactions. Using a combination of fluorescence labeling and stopped-flow spectroscopy, we have investigated the basis for these interactions. Specifically, in order to study P450--CPR interactions, a single reactive cysteine was introduced in to a genetically engineered variant of CYP2B4 (C79SC152S) at each of seven strategically selected surface-exposed positions. Each of these cysteine residues was modified by reaction with fluorescein-5-maleimide (FM), and the CYP2B4-FM variants were then used to determine the K(d) of the complex by monitoring fluorescence enhancement in the presence of CPR. Furthermore, the intrinsic K(m) values of the CYP2B4 variants for CPR were measured, and stopped-flow spectroscopy was used to determine the intrinsic kinetics and the extent of reduction of the ferric P450 mutants to the ferrous P450--CO adduct by CPR. A comparison of the results from these three approaches reveals that the sites on P450 exhibiting the greatest changes in fluorescence intensity upon binding CPR are associated with the greatest increases in the K(m) values of the P450 variants for CPR and with the greatest decreases in the rates and extents of reduced P450--CO formation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.