ArticlePloS one2013
A large-scale allosteric transition in cytochrome P450 3A4 revealed by luminescence resonance energy transfer (LRET).
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Identification of the contact region responsible for the formation of the homomeric CYP1A2•CYP1A2 complex.The Biochemical journal · 2021Article
- Midazolam as a Probe for Drug-Drug Interactions Mediated by CYP3A4: Homotropic Allosteric Mechanism of Site-Specific Hydroxylation.Biochemistry · 2021Article
- Correction to "Allosteric Interactions in Human Cytochrome P450 CYP3A4: The Role of Phenylalanine 213".Biochemistry · 2019Article
- Allosteric Interactions in Human Cytochrome P450 CYP3A4: The Role of Phenylalanine 213.Biochemistry · 2019Article
- Toward a systems approach to the human cytochrome P450 ensemble: interactions between CYP2D6 and CYP2E1 and their functional consequences.The Biochemical journal · 2017Article
- High-Level Production and Properties of the Cysteine-Depleted Cytochrome P450 3A4.Biochemistry · 2017Article
- Physical Studies of P450-P450 Interactions: Predicting Quaternary Structures of P450 Complexes in Membranes from Their X-ray Crystal Structures.Frontiers in pharmacology · 2017Review
- Cyclic Glucans Enhance Solubility of Bioavailable Flavonoids.Molecules (Basel, Switzerland) · 2016Review
- Conformational Mobility in Cytochrome P450 3A4 Explored by Pressure-Perturbation EPR Spectroscopy.Biophysical journal · 2016Article
- 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
- Article
- Interactions between CYP3A4 and Dietary Polyphenols.Oxidative medicine and cellular longevity · 2015Review
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
Abstract
Effector-induced allosteric transitions in cytochrome P450 3A4 (CYP3A4) were investigated by luminescence resonance energy transfer (LRET) between two SH-reactive probes attached to various pairs of distantly located cysteine residues, namely the double-cysteine mutants CYP3A4(C64/C468), CYP3A4(C377/C468) and CYP3A4(C64/C121). Successive equimolar labeling of these proteins with the phosphorescent probe erythrosine iodoacetamide (donor) and the near-infrared fluorophore DY-731 maleimide (acceptor) allowed us to establish donor/acceptor pairs sensitive to conformational motions. The interactions of all three double-labeled mutants with the allosteric activators α-naphthoflavone and testosterone resulted in an increase in the distance between the probes. A similar effect was elicited by cholesterol. These changes in distance vary from 1.3 to 8.5 Å, depending on the position of the donor/acceptor pair and the nature of the effector. In contrast, the changes in the interprobe distance caused by such substrates as bromocriptine or 1-pyrenebutanol were only marginal. Our results provide a decisive support to the paradigm of allosteric modulation of CYP3A4 and indicate that the conformational transition caused by allosteric effectors increases the spatial separation between the beta-domain of the enzyme (bearing residues Cys64 and Cys377) and the alpha-domain, where Cys121 and Cys468 are located.
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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.