ArticleBiochemistry2007
Global analysis of protein-protein interactions reveals multiple CYP2E1-reductase complexes.
Article in Biochemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Functional characterization of CYP1 enzymes: Complex formation, membrane localization and function.Journal of inorganic biochemistry · 2023Article
- Complex Cytochrome P450 Kinetics Due to Multisubstrate Binding and Sequential Metabolism. Part 1. Theoretical Considerations.Drug metabolism and disposition: the biological fate of chemicals · 2021Article
- Heteromeric complex formation between human cytochrome P450 CYP1A1 and heme oxygenase-1.The Biochemical journal · 2021Article
- Unravelling the intricate cooperativity of subunit gating in P2X2 ion channels.Scientific reports · 2020Article
- Transcriptomic Analysis Reveals the Roles of Detoxification Systems in Response to Mercury inBiomolecules · 2019Article
- Structural and Functional Studies of the Membrane-Binding Domain of NADPH-Cytochrome P450 Oxidoreductase.Biochemistry · 2019Article
- Characterization of Interactions Among CYP1A2, CYP2B4, and NADPH-cytochrome P450 Reductase: Identification of Specific Protein Complexes.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Aerobic Respiration: Criticism of the Proton-centric Explanation Involving Rotary Adenosine Triphosphate Synthesis, Chemiosmosis Principle, Proton Pumps and Electron Transport Chain.Biochemistry insights · 2018Article
- Assembly of Dynamic P450-Mediated Metabolons-Order Versus Chaos.Current molecular biology reports · 2017Review
- Physical Studies of P450-P450 Interactions: Predicting Quaternary Structures of P450 Complexes in Membranes from Their X-ray Crystal Structures.Frontiers in pharmacology · 2017Review
- The functional effects of physical interactions involving cytochromes P450: putative mechanisms of action and the extent of these effects in biological membranes.Drug metabolism reviews · 2016Review
- Immobilized Cytochrome P450 for Monitoring of P450-P450 Interactions and Metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Role of protein-protein interactions in cytochrome P450-mediated drug metabolism and toxicity.Chemical research in toxicology · 2014Review
- Correlating structure and function of drug-metabolizing enzymes: progress and ongoing challenges.Drug metabolism and disposition: the biological fate of chemicals · 2014Review
- Method of continuous variations: applications of job plots to the study of molecular associations in organometallic chemistry.Angewandte Chemie (International ed. in English) · 2013Review
- Effect of homomeric P450-P450 complexes on P450 function.The Biochemical journal · 2012Article
- Formation of P450 · P450 complexes and their effect on P450 function.Pharmacology & therapeutics · 2012Review
- Beta sheet 2-alpha helix C loop of cytochrome P450 reductase serves as a docking site for redox partners.Biochimica et biophysica acta · 2010Article
- Functional interactions between cytochromes P450 1A2 and 2B4 require both enzymes to reside in the same phospholipid vesicle: evidence for physical complex formation.The Journal of biological chemistry · 2010Article
- Cooperative properties of cytochromes P450.Pharmacology & therapeutics · 2009Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Although a single binary functional complex between cytochrome P450 (P450 or CYP for a specific isoform) and cytochrome P450 reductase (CPR) has been generally accepted in the literature, this simple model failed to explain the experimentally observed catalytic activity of recombinant CYP2E1 in dependence on the total concentration of the added CPR-K56Q mutant. Our rejection of the simplest 1:1 binding model was based on two independent lines of experimental evidence. First, under the assumption of the 1:1 binding model, separate analyses of titration curves obtained while varying either P450 or CPR concentrations individually produced contradictory results. Second, an asymmetric Job plot suggested the existence of higher order molecular complexes. To identify the most probable complexation mechanism, we generated a comprehensive data set where the concentrations of both P450 and P450 were varied simultaneously, rather than one at a time. The resulting two-dimensional data were globally fit to 32 candidate mechanistic models, involving the formation of binary, ternary, and quaternary P450.CPR complexes, in the absence or presence or P450 and CPR homodimers. Of the 32 candidate models (mechanisms), two models were approximately equally successful in explaining our experimental data. The first plausible model involves the binary complex P450.CPR, the quaternary complex (P450)2.(CPR)2, and the homodimer (P450)2. The second plausible model additionally involves a weakly bound ternary complex (P450)2.CPR. Importantly, only the binary complex P450.CPR seems catalytically active in either of the two most probable mechanisms.
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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.