ArticleNature communications2021
Biased cytochrome P450-mediated metabolism via small-molecule ligands binding P450 oxidoreductase.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 70 citations in OpenAlex.
- Single-molecule kinetic exploration of functional sub-states in an evolving phosphotriesterase.Nature communications · 2026Article
- A Novel POR G88S Mutation Causes Severe PORD and Establishes a Critical Pharmacogenomic Risk Profile.The Journal of clinical endocrinology and metabolism · 2026Article
- Chromatin boundary permeability is controlled by CTCF conformational ensembles.bioRxiv : the preprint server for biology · 2026Article
- Pyridine indole hybrids as novel potent CYP17A1 inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Heterologous Production of the Structurally Complex Diterpenoid Forskolin inBioengineering (Basel, Switzerland) · 2025Article
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- Modulation of insulin aggregation by betaine and proline directly observed via real-time super-resolution microscopy.Protein science : a publication of the Protein Society · 2025Article
- Deep learning-assisted analysis of single-particle tracking for automated correlation between diffusion and function.Nature methods · 2025Article
- Nanoparticles with curcumin and piperine modulate steroid biosynthesis in prostate cancer.Scientific reports · 2025Article
- The Multifunctional Preprotein Binding Domain of SecA.Chembiochem : a European journal of chemical biology · 2024Article
- P450Rdb: A manually curated database of reactions catalyzed by cytochrome P450 enzymes.Journal of advanced research · 2024Article
- Large-scale genome-wide association studies reveal the genetic causal etiology between air pollutants and autoimmune diseases.Journal of translational medicine · 2024Article
- Elucidating the Mechanism of Metabolism of Cannabichromene by Human Cytochrome P450s.Journal of natural products · 2024Article
- Global organization of phenylpropanoid and anthocyanin pathways revealed by proximity labeling of trans-cinnamic acid 4-hydroxylase inFrontiers in plant science · 2024Article
- Article
- Engineered human liver based on pullulan-dextran hydrogel promotes mice survival after liver failure.Materials today. Bio · 2023Article
- Single-Particle Tracking ofBiomolecules · 2023Article
- Enhanced hexamerization of insulin via assembly pathway rerouting revealed by single particle studies.Communications biology · 2023Article
- Genetic Perturbation Alters Functional Substates in Alkaline Phosphatase.Journal of the American Chemical Society · 2023Article
- Loss of Protein Stability and Function Caused by P228L Variation in NADPH-Cytochrome P450 Reductase Linked to Lower Testosterone Levels.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolic control is mediated by the dynamic assemblies and function of multiple redox enzymes. A key element in these assemblies, the P450 oxidoreductase (POR), donates electrons and selectively activates numerous (>50 in humans and >300 in plants) cytochromes P450 (CYPs) controlling metabolism of drugs, steroids and xenobiotics in humans and natural product biosynthesis in plants. The mechanisms underlying POR-mediated CYP metabolism remain poorly understood and to date no ligand binding has been described to regulate the specificity of POR. Here, using a combination of computational modeling and functional assays, we identify ligands that dock on POR and bias its specificity towards CYP redox partners, across mammal and plant kingdom. Single molecule FRET studies reveal ligand binding to alter POR conformational sampling, which results in biased activation of metabolic cascades in whole cell assays. We propose the model of biased metabolism, a mechanism akin to biased signaling of GPCRs, where ligand binding on POR stabilizes different conformational states that are linked to distinct metabolic outcomes. Biased metabolism may allow designing pathway-specific therapeutics or personalized food suppressing undesired, disease-related, metabolic pathways.
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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.