ArticleProceedings of the National Academy of Sciences of the United States of America2015
Unveiling the crucial intermediates in androgen production.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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
45 citing papers in PubMed.
- Mechanistic and spectroscopic characterization of human CYP17A1 in Nanodiscs.Journal of inorganic biochemistry · 2026Review
- Cytochrome P450The Journal of biological chemistry · 2025Article
- Modulation of heme peroxo nucleophilicities with axial ligands reveal key insights into the mechanistic landscape of nitric oxide synthase.Chemical science · 2025Article
- Optical annealing of peroxo-ferric intermediates in CYP17A1 and product formation.Journal of inorganic biochemistry · 2024Article
- Dioxygenase Chemistry in Nucleophilic Aldehyde Deformylations Utilizing Dicopper OJournal of the American Chemical Society · 2024Article
- Updates on Mechanisms of Cytochrome P450 Catalysis of Complex Steroid Oxidations.International journal of molecular sciences · 2024Review
- Cryoradiolysis of oxygenated cytochrome P450 17A1 with lyase substrates generates expected products.Journal of inorganic biochemistry · 2024Article
- SelectiveACS catalysis · 2024Article
- Oxygen-18 Labeling Reveals a Mixed Fe-O Mechanism in the Last Step of Cytochrome P450 51 Sterol 14α-Demethylation.Angewandte Chemie (International ed. in English) · 2024Article
- In Situ Structural Observation of a Substrate- and Peroxide-Bound High-Spin Ferric-Hydroperoxo Intermediate in the P450 Enzyme CYP121.Journal of the American Chemical Society · 2023Article
- Solvent isotope effects in the catalytic cycle of P450 CYP17A1: Computational modeling of the hydroxylation and lyase reactions.Journal of inorganic biochemistry · 2023Article
- Engineering C-C Bond Cleavage Activity into a P450 Monooxygenase Enzyme.Journal of the American Chemical Society · 2023Article
- Investigating the Active Oxidants Involved in Cytochrome P450 Catalyzed Sulfoxidation Reactions.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Importance of Asparagine 202 in Manipulating Active Site Structure and Substrate Preference for Human CYP17A1.Biochemistry · 2022Article
- Diverse reactions catalyzed by cytochrome P450 and biosynthesis of steroid hormone.Biophysics and physicobiology · 2022Article
- Mechanism of the Clinically Relevant E305G Mutation in Human P450 CYP17A1.Biochemistry · 2021Article
- Steroidogenic cytochrome P450 17A1 structure and function.Molecular and cellular endocrinology · 2021Review
- Substrate-Specific Allosteric Effects on the Enhancement of CYP17A1 Lyase Efficiency by CytochromeJournal of the American Chemical Society · 2021Article
- Nanodiscs: A toolkit for membrane protein science.Protein science : a publication of the Protein Society · 2021Review
- P450 CYP17A1 Variant with a Disordered Proton Shuttle Assembly Retains Peroxo-Mediated Lyase Efficiency.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
Ablation of androgen production through surgery is one strategy against prostate cancer, with the current focus placed on pharmaceutical intervention to restrict androgen synthesis selectively, an endeavor that could benefit from the enhanced understanding of enzymatic mechanisms that derives from characterization of key reaction intermediates. The multifunctional cytochrome P450 17A1 (CYP17A1) first catalyzes the typical hydroxylation of its primary substrate, pregnenolone (PREG) and then also orchestrates a remarkable C17-C20 bond cleavage (lyase) reaction, converting the 17-hydroxypregnenolone initial product to dehydroepiandrosterone, a process representing the first committed step in the biosynthesis of androgens. Now, we report the capture and structural characterization of intermediates produced during this lyase step: an initial peroxo-anion intermediate, poised for nucleophilic attack on the C20 position by a substrate-associated H-bond, and the crucial ferric peroxo-hemiacetal intermediate that precedes carbon-carbon (C-C) bond cleavage. These studies provide a rare glimpse at the actual structural determinants of a chemical transformation that carries profound physiological consequences.
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.