ArticleMolecular biology and evolution2021
Concerning P450 Evolution: Structural Analyses Support Bacterial Origin of Sterol 14α-Demethylases.
Article in Molecular biology and evolution, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Supporting activities of cognate redox partners for sterol-metabolizing P450 enzymes in Mycobacterium neoaurum.The Journal of biological chemistry · 2026Article
- Complex Roles of Insect Cytochrome P450s in Chemical Adaptation.International journal of biological sciences · 2026Review
- A plant-specific cytochromeScience advances · 2025Article
- Unique Structural Features Relate to Evolutionary Adaptation of Cytochrome P450 in the Abyssal Zone.International journal of molecular sciences · 2025Article
- Comprehensive Review on Plant Cytochrome P450 Evolution: Copy Number, Diversity, and Motif Analysis From Chlorophyta to Dicotyledoneae.Genome biology and evolution · 2024Review
- Imidazoles and Quaternary Ammonium Compounds as Effective Therapies against (Multidrug-Resistant) Bacterial Wound Infections.Antibiotics (Basel, Switzerland) · 2024Article
- Design, Synthesis, and Antifungal Activities of Phenylpyrrole Analogues Based on Alkaloid Lycogalic Acid.Molecules (Basel, Switzerland) · 2024Article
- Identification of Potent and Selective Inhibitors ofJournal of medicinal chemistry · 2024Article
- Druggable Sterol Metabolizing Enzymes in Infectious Diseases: Cell Targets to Therapeutic Leads.Biomolecules · 2024Review
- Genome-Wide Analysis of the Cytochrome P450 Monooxygenases in the Lichenized Fungi of the ClassMicroorganisms · 2023Article
- Pezizomycetes Genomes Reveal Diverse P450 Complements Characteristic of Saprotrophic and Ectomycorrhizal Lifestyles.Journal of fungi (Basel, Switzerland) · 2023Article
- Structural modeling of cytochrome P450 51 from a deep-sea fish points to a novel structural feature in other CYP51s.Journal of inorganic biochemistry · 2023Article
- De novo cholesterol biosynthesis in bacteria.Nature communications · 2023Article
- Evolution of Cytochrome P450 Enzymes and Their Redox Partners in Archaea.International journal of molecular sciences · 2023Article
- Article
- Unravelling the role of transient redox partner complexes in P450 electron transfer mechanics.Scientific reports · 2022Article
- Lifestyles Shape the Cytochrome P450 Repertoire of the Bacterial PhylumInternational journal of molecular sciences · 2022Article
- Structural insights into 3Fe-4S ferredoxins diversity inFrontiers in molecular biosciences · 2022Article
- Relaxed Substrate Requirements of Sterol 14α-Demethylase fromJournal of medicinal chemistry · 2021Article
- Roles for Structural Biology in the Discovery of Drugs and Agrochemicals Targeting Sterol 14α-Demethylases.Journal of fungi (Basel, Switzerland) · 2021Review
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Sterol biosynthesis, primarily associated with eukaryotic kingdoms of life, occurs as an abbreviated pathway in the bacterium Methylococcus capsulatus. Sterol 14α-demethylation is an essential step in this pathway and is catalyzed by cytochrome P450 51 (CYP51). In M. capsulatus, the enzyme consists of the P450 domain naturally fused to a ferredoxin domain at the C-terminus (CYP51fx). The structure of M. capsulatus CYP51fx was solved to 2.7 Å resolution and is the first structure of a bacterial sterol biosynthetic enzyme. The structure contained one P450 molecule per asymmetric unit with no electron density seen for ferredoxin. We connect this with the requirement of P450 substrate binding in order to activate productive ferredoxin binding. Further, the structure of the P450 domain with bound detergent (which replaced the substrate upon crystallization) was solved to 2.4 Å resolution. Comparison of these two structures to the CYP51s from human, fungi, and protozoa reveals strict conservation of the overall protein architecture. However, the structure of an "orphan" P450 from nonsterol-producing Mycobacterium tuberculosis that also has CYP51 activity reveals marked differences, suggesting that loss of function in vivo might have led to alterations in the structural constraints. Our results are consistent with the idea that eukaryotic and bacterial CYP51s evolved from a common cenancestor and that early eukaryotes may have recruited CYP51 from a bacterial source. The idea is supported by bioinformatic analysis, revealing the presence of CYP51 genes in >1,000 bacteria from nine different phyla, >50 of them being natural CYP51fx fusion proteins.
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