ArticleThe Journal of biological chemistry2019
Human cytochrome P450 enzymes bind drugs and other substrates mainly through conformational-selection modes.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Binding Site Vectors Enable Mapping of Cytochrome P450 Functional Landscapes.Journal of chemical information and modeling · 2026Article
- Molecular dynamics simulations elucidate the role of the F-F' loop in substrate entry into CYP3A4.Communications chemistry · 2026Article
- Cross-Species Multitask Learning with Molecular and ADME Descriptors for Liver Microsomal Metabolic Stability.Computational and structural biotechnology journal · 2026Article
- Aging, ROS, and cellular senescence: a trilogy in the progression of liver fibrosis.Biogerontology · 2024Review
- A Computational Pipeline Observes the Flexibility and Dynamics of Plant Cytochrome P450 Binding Sites.International journal of molecular sciences · 2024Article
- Roles of Individual Human Cytochrome P450 Enzymes in Drug Metabolism.Pharmacological reviews · 2024Review
- Ninety-eight semesters of cytochrome P450 enzymes and related topics-What have I taught and learned?The Journal of biological chemistry · 2024Article
- Water Exchange from the Buried Binding Sites of Cytochrome P450 Enzymes 1A2, 2D6, and 3A4 Correlates with Conformational Fluctuations.Molecules (Basel, Switzerland) · 2024Article
- Article
- Differential Effects of Clotrimazole on X-Ray Crystal Structures of Human Cytochromes P450 3A5 and 3A4.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Induced Fit Describes Ligand Binding to Membrane-Associated Cytochrome P450 3A4.Molecular pharmacology · 2023Article
- Low molecular weight ligands bind to CYP3A4 via a branched induced fit mechanism: Implications for OArchives of biochemistry and biophysics · 2023Article
- Getting Deeper into the Molecular Events of Heme Binding Mechanisms: A Comparative Multi-level Computational Study of HasAsm and HasAyp Hemophores.Inorganic chemistry · 2022Article
- Biocompatibility Study of Curcumin-Loaded Pluronic F127 Nanoformulation (NanoCUR) against the Embryonic Development of Zebrafish (Molecules (Basel, Switzerland) · 2022Article
- Molecular Lego of Human Cytochrome P450: The Key Role of Heme Domain Flexibility for the Activity of the Chimeric Proteins.International journal of molecular sciences · 2022Article
- Article
- Roles of cytochrome P450 enzymes in pharmacology and toxicology: Past, present, and future.Advances in pharmacology (San Diego, Calif.) · 2022Article
- The ubiquitin hydrolase OTUB1 promotes glioma cell stemness via suppressing ferroptosis through stabilizing SLC7A11 protein.Bioengineered · 2021Article
- Induced fit versus conformational selection: From rate constants to fluxes… and back to rate constants.Pharmacology research & perspectives · 2021Article
- Development of Robust Quantitative Structure-Activity Relationship Models for CYP2C9, CYP2D6, and CYP3A4 Catalysis and Inhibition.Drug metabolism and disposition: the biological fate of chemicals · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cytochrome P450 (P450) enzymes are major catalysts involved in the oxidations of most drugs, steroids, carcinogens, fat-soluble vitamins, and natural products. The binding of substrates to some of the 57 human P450s and other mammalian P450s is more complex than a two-state system and has been proposed to involve mechanisms such as multiple ligand occupancy, induced-fit, and conformational-selection. Here, we used kinetic analysis of binding with multiple concentrations of substrates and computational modeling of these data to discern possible binding modes of several human P450s. We observed that P450 2D6 binds its ligand rolapitant in a mechanism involving conformational-selection. P450 4A11 bound the substrate lauric acid via conformational-selection, as did P450 2C8 with palmitic acid. Binding of the steroid progesterone to P450 21A2 was also best described by a conformational-selection model. Hexyl isonicotinate binding to P450 2E1 could be described by either a conformational-selection or an induced-fit model. Simulation of the binding of the ligands midazolam, bromocriptine, testosterone, and ketoconazole to P450 3A4 was consistent with an induced-fit or a conformational-selection model, but the concentration dependence of binding rates for varying both P450 3A4 and midazolam concentrations revealed discordance in the parameters, indicative of conformational-selection. Binding of the P450s 2C8, 2D6, 3A4, 4A11, and 21A2 was best described by conformational-selection, and P450 2E1 appeared to fit either mode. These findings highlight the complexity of human P450-substrate interactions and that conformational-selection is a dominant feature of many of these interactions.
Indexed as
Identifiers
What OpenQuestion holds
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.