ArticleProceedings of the National Academy of Sciences of the United States of America2014
Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.
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Who cites it
123 citing papers in PubMed, 277 citations in OpenAlex.
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- The dual role of azoles: lifesaving antifungals and drivers of resistance - a One Health perspective.Nature communications · 2026Review
- Regulation of ABC Transporters and Ergosterol Biosynthesis by the Transcription Factor FvADS-1 Controls Azole Resistance and Virulence inJournal of fungi (Basel, Switzerland) · 2026Article
- Complex Roles of Insect Cytochrome P450s in Chemical Adaptation.International journal of biological sciences · 2026Review
- In vitro and in vivo efficacy of the antimycobacterial molecule SQ109 against the human pathogenic fungus, Cryptococcus neoformans.PLoS neglected tropical diseases · 2025Article
- Natural Polymorphic Variants in the CYP450 Superfamily: A Review of Potential Structural Mechanisms and Functional Consequences.International journal of molecular sciences · 2025Review
- Exploring Long Arm Amide-Linked Side Chains in the Design of Antifungal Azole Inhibitors of Sterol 14α-Demethylase (CYP51).Journal of medicinal chemistry · 2025Article
- The Nature of Nanodisc Lipids Influences Fragment-Based Drug Discovery Results.Chemical biology & drug design · 2025Article
- Theoretical Study on the Metabolic Mechanism of Heptachlor in Human Cytochrome P450 Enzymes.International journal of molecular sciences · 2025Article
- Properties of "Stable" Mosquito Cytochrome P450 Enzymes.Insects · 2025Article
- Intrinsic resistance to short-tailed azoles in the basal fungusFrontiers in microbiology · 2025Article
- Bacterial expression, purification, and characterization of human cytochrome P450 3A4 without N-terminal modifications.Archives of biochemistry and biophysics · 2024Article
- Topology surveillance of the lanosterol demethylase CYP51A1 by signal peptide peptidase.Journal of cell science · 2024Article
- The Molecular Basis of the Intrinsic and Acquired Resistance to Azole Antifungals inJournal of fungi (Basel, Switzerland) · 2024Article
- N-substituted-4-(pyridin-4-ylalkyl)piperazine-1-carboxamides and related compounds as Leishmania CYP51 and CYP5122A1 inhibitors.Bioorganic & medicinal chemistry · 2024Article
- A flexible linker of 8-amino acids between the membrane binding segment and the FMN domain of cytochrome P450 reductase is necessary for optimal activity.Journal of inorganic biochemistry · 2024Article
- Design, Synthesis, and Antifungal Activities of Phenylpyrrole Analogues Based on Alkaloid Lycogalic Acid.Molecules (Basel, Switzerland) · 2024Article
- Effect of Conformational Variability on the Drug Resistance ofACS omega · 2024Article
- Innovations in Antifungal Drug Discovery among Cell Envelope Synthesis Enzymes through Structural Insights.Journal of fungi (Basel, Switzerland) · 2024Review
- Design, synthesis, docking studies and bioactivity evaluation of 1,2,3-triazole eugenol derivatives.Future medicinal chemistry · 2024Article
63 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Bitopic integral membrane proteins with a single transmembrane helix play diverse roles in catalysis, cell signaling, and morphogenesis. Complete monospanning protein structures are needed to show how interaction between the transmembrane helix and catalytic domain might influence association with the membrane and function. We report crystal structures of full-length Saccharomyces cerevisiae lanosterol 14α-demethylase, a membrane monospanning cytochrome P450 of the CYP51 family that catalyzes the first postcyclization step in ergosterol biosynthesis and is inhibited by triazole drugs. The structures reveal a well-ordered N-terminal amphipathic helix preceding a putative transmembrane helix that would constrain the catalytic domain orientation to lie partly in the lipid bilayer. The structures locate the substrate lanosterol, identify putative substrate and product channels, and reveal constrained interactions with triazole antifungal drugs that are important for drug design and understanding drug resistance.
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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.