ArticleThe Journal of biological chemistry2014
Structures of human steroidogenic cytochrome P450 17A1 with substrates.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 122 citations in OpenAlex.
- Insilico Analysis of CYP17A1 in the Pathogenesis of Polycystic Ovarian Syndrome by Molecular Dynamics and Genotypic Characterization.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Mechanistic and spectroscopic characterization of human CYP17A1 in Nanodiscs.Journal of inorganic biochemistry · 2026Review
- Dihydrotanshinone as a Natural Product-Based CYP17A1 Lyase Inhibitor for Hyperandrogenic Disorders.Biomolecules · 2026Article
- Human Cytochrome P450 Cancer-Related Metabolic Activities and Gene Polymorphisms: A Review.Cells · 2024Review
- Optical annealing of peroxo-ferric intermediates in CYP17A1 and product formation.Journal of inorganic biochemistry · 2024Article
- Updates on Mechanisms of Cytochrome P450 Catalysis of Complex Steroid Oxidations.International journal of molecular sciences · 2024Review
- Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450.Biomolecules · 2024Article
- Abiraterone Acetate Complexes with Biometals: Synthesis, Characterization in Solid and Solution, and the Nature of Chemical Bonding.Pharmaceutics · 2023Article
- Transcriptional changes in multiple endocrine organs from lethal cases of COVID-19.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Recombinant Technologies Facilitate Drug Metabolism, Pharmacokinetics, and General Biomedical Research.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Non-steroidal CYP17A1 Inhibitors: Discovery and Assessment.Journal of medicinal chemistry · 2023Review
- Hydroxylation and lyase reactions of steroids catalyzed by mouse cytochrome P450 17A1 (Cyp17a1).Journal of inorganic biochemistry · 2023Article
- Crosstalk between ferroptosis and steroid hormone signaling in gynecologic cancers.Frontiers in molecular biosciences · 2023Review
- Steroid 17α-hydroxylase/17, 20-lyase (cytochrome P450 17A1).Methods in enzymology · 2023Article
- Four Decades of Cytochrome P450 2B Research: From Protein Adducts to Protein Structures and Beyond.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- In Silico Identification of Promising New Pyrazole Derivative-Based Small Molecules for Modulating CRMP2, C-RAF, CYP17, VEGFR, C-KIT, and HDAC-Application towards Cancer Therapeutics.Current issues in molecular biology · 2022Article
- Follicle isolation methods reveal plasticity of granulosa cell steroidogenic capacity during mouse in vitro follicle growth.Molecular human reproduction · 2022Article
- Importance of Asparagine 202 in Manipulating Active Site Structure and Substrate Preference for Human CYP17A1.Biochemistry · 2022Article
- Hexaconazole exposure ravages biosynthesis pathway of steroid hormones: revealed by molecular dynamics and interaction.Toxicology research · 2022Article
- Synthesis and Structure-Activity Relationships of Novel Non-Steroidal CYP17A1 Inhibitors as Potential Prostate Cancer Agents.Biomolecules · 2022Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The human cytochrome P450 17A1 (CYP17A1) enzyme operates at a key juncture of human steroidogenesis, controlling the levels of mineralocorticoids influencing blood pressure, glucocorticoids involved in immune and stress responses, and androgens and estrogens involved in development and homeostasis of reproductive tissues. Understanding CYP17A1 multifunctional biochemistry is thus integral to treating prostate and breast cancer, subfertility, blood pressure, and other diseases. CYP17A1 structures with all four physiologically relevant steroid substrates suggest answers to four fundamental aspects of CYP17A1 function. First, all substrates bind in a similar overall orientation, rising ∼60° with respect to the heme. Second, both hydroxylase substrates pregnenolone and progesterone hydrogen bond to Asn(202) in orientations consistent with production of 17α-hydroxy major metabolites, but functional and structural evidence for an A105L mutation suggests that a minor conformation may yield the minor 16α-hydroxyprogesterone metabolite. Third, substrate specificity of the subsequent 17,20-lyase reaction may be explained by variation in substrate height above the heme. Although 17α-hydroxyprogesterone is only observed farther from the catalytic iron, 17α-hydroxypregnenolone is also observed closer to the heme. In conjunction with spectroscopic evidence, this suggests that only 17α-hydroxypregnenolone approaches and interacts with the proximal oxygen of the catalytic iron-peroxy intermediate, yielding efficient production of dehydroepiandrosterone as the key intermediate in human testosterone and estrogen synthesis. Fourth, differential positioning of 17α-hydroxypregnenolone offers a mechanism whereby allosteric binding of cytochrome b5 might selectively enhance the lyase reaction. In aggregate, these structures provide a structural basis for understanding multiple key reactions at the heart of human steroidogenesis.
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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.