ArticleThe Journal of biological chemistry2010
Functional interactions between cytochromes P450 1A2 and 2B4 require both enzymes to reside in the same phospholipid vesicle: evidence for physical complex formation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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
30 citing papers in PubMed, 44 citations in OpenAlex.
- Functional characterization of CYP1 enzymes: Complex formation, membrane localization and function.Journal of inorganic biochemistry · 2023Article
- The Influence of Lipid Microdomain Heterogeneity on Protein-Protein Interactions: Proteomic Analysis of Co-Immunoprecipitated Binding Partners of P450 1A2 and P450 3A in Rat Liver Microsomes.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Identification of the contact region responsible for the formation of the homomeric CYP1A2•CYP1A2 complex.The Biochemical journal · 2021Article
- Effects of alcohol-induced increase in CYP2E1 content in human liver microsomes on the activity and cooperativity of CYP3A4.Archives of biochemistry and biophysics · 2021Article
- Heteromeric complex formation between human cytochrome P450 CYP1A1 and heme oxygenase-1.The Biochemical journal · 2021Article
- Toward a systems approach to cytochrome P450 ensemble: interactions of CYP2E1 with other P450 species and their impact on CYP1A2.The Biochemical journal · 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
- Toward a systems approach to the human cytochrome P450 ensemble: interactions between CYP2D6 and CYP2E1 and their functional consequences.The Biochemical journal · 2017Article
- Nanodiscs in Membrane Biochemistry and Biophysics.Chemical reviews · 2017Review
- Advances in the Understanding of Protein-Protein Interactions in Drug Metabolizing Enzymes through the Use of Biophysical Techniques.Frontiers in pharmacology · 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
- Cytochrome P450 Organization and Function Are Modulated by Endoplasmic Reticulum Phospholipid Heterogeneity.Drug metabolism and disposition: the biological fate of chemicals · 2016Review
- 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
- The Role of Protein-Protein and Protein-Membrane Interactions on P450 Function.Drug metabolism and disposition: the biological fate of chemicals · 2016Review
- Interaction Between Polymorphisms of IFN-γ and MICA Correlated with Hepatocellular Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- Environmentally persistent free radical-containing particulate matter competitively inhibits metabolism by cytochrome P450 1A2.Toxicology and applied pharmacology · 2015Article
- Interactions among cytochromes P450 in microsomal membranes: oligomerization of cytochromes P450 3A4, 3A5, and 2E1 and its functional consequences.The Journal of biological chemistry · 2015Article
- Cytochrome P450 system proteins reside in different regions of the endoplasmic reticulum.The Biochemical journal · 2014Article
- Role of protein-protein interactions in cytochrome P450-mediated drug metabolism and toxicity.Chemical research in toxicology · 2014Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Previous studies have shown that the combined presence of two cytochrome P450 enzymes (P450s) can affect the function of both enzymes, results that are consistent with the formation of heteromeric P450.P450 complexes. The goal of this study was to provide direct evidence for a physical interaction between P450 1A2 (CYP1A2) and P450 2B4 (CYP2B4), by determining if the interactions required both enzymes to reside in the same lipid vesicles. When NADPH-cytochrome P450 reductase (CPR) and a single P450 were incorporated into separate vesicles, extremely slow reduction rates were observed, demonstrating that the enzymes were anchored in the vesicles. Next, several reconstituted systems were prepared: 1) CPR.CYP1A2, 2) CPR.CYP2B4, 3) a mixture of CPR.CYP1A2 vesicles with CPR.CYP2B4 vesicles, and 4) CPR.CYP1A2.CYP2B4 in the same vesicles (ternary system). When in the ternary system, CYP2B4-mediated metabolism was significantly inhibited, and CYP1A2 activities were stimulated by the presence of the alternate P450. In contrast, P450s in separate vesicles were unable to interact. These data demonstrate that P450s must be in the same vesicles to alter metabolism. Additional evidence for a physical interaction among CPR, CYP1A2, and CYP2B4 was provided by cross-linking with bis(sulfosuccinimidyl) suberate. The results showed that after cross-linking, antibody to CYP1A2 was able to co-immunoprecipitate CYP2B4 but only when both proteins were in the same phospholipid vesicles. These results clearly demonstrate that the alterations in P450 function require both P450s to be present in the same vesicles and support a mechanism whereby P450s form a physical complex in the membrane.
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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.