ArticleThe Journal of steroid biochemistry and molecular biology2018
Testosterone complex and non-steroidal ligands of human aromatase.
Article in The Journal of steroid biochemistry and molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 64 citations in OpenAlex.
- Synthesis and multi-target antiproliferative evaluation of novel 1,2,4-triazole-3-thione analogues against breast cancer:RSC advances · 2025Article
- Integrated Virtual Screening Approach Identifies New CYP19A1 Inhibitors.Journal of chemical information and modeling · 2025Article
- Zhuangyao Jianshen pill ameliorates testosterone-induced benign postatic hyperplasia in rats.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- Computational Binding Study Hints at Ecdysone 20-Mono-Oxygenase as the Hitherto Unknown Target for Ring C-Seco Limonoid-Type Insecticides.Molecules (Basel, Switzerland) · 2024Article
- Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450.Biomolecules · 2024Article
- Pyridine based dual binding site aromatase (CYP19A1) inhibitors.RSC medicinal chemistry · 2023Article
- Interaction of letrozole and its degradation products with aromatase: chemometric assessment of kinetics and structure-based binding validation.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Targeting allosteric sites of human aromatase: a comprehensiveJournal of enzyme inhibition and medicinal chemistry · 2021Article
- Mechanisms of allosteric and mixed mode aromatase inhibitors.RSC chemical biology · 2021Article
- Testosterone and the brain: from cognition to autism.Physiological research · 2020Review
- Reconsidering Aromatase for Breast Cancer Treatment: New Roles for an Old Target.Molecules (Basel, Switzerland) · 2020Review
- Slow-, Tight-Binding Inhibition of CYP17A1 by Abiraterone Redefines Its Kinetic Selectivity and Dosing Regimen.The Journal of pharmacology and experimental therapeutics · 2020Article
- Dynamics and Mechanism of Binding of Androstenedione to Membrane-Associated Aromatase.Biochemistry · 2020Article
- Steroids and TRP Channels: A Close Relationship.International journal of molecular sciences · 2020Review
- Mechanistic Insights into the Regio- and Stereoselectivities of Testosterone and Dihydrotestosterone Hydroxylation Catalyzed by CYP3A4 and CYP19A1.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
- Anaerobic bacteria need their vitamin BProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Phosphorylation of human placental aromatase CYP19A1.The Biochemical journal · 2019Article
- Organoruthenium(II) Complexes Bearing an Aromatase Inhibitor: Synthesis, Characterization,Organometallics · 2019Article
- Human cytochrome P450 enzymes 5-51 as targets of drugs and natural and environmental compounds: mechanisms, induction, and inhibition - toxic effects and benefits.Drug metabolism reviews · 2018Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cytochrome P450 aromatase (AROM) catalyzes the biosynthesis of estrogen from androgen. Previously crystal structures of human AROM in complex with the substrate androstenedione, and inhibitors exemestane, as well as the newly designed steroidal compounds, have been reported. Here we report the first crystal structure of testosterone complex of human placental AROM. Testosterone binds at the androgen-specific heme distal pocket. The polar and hydrophobic interactions with the surrounding residues resemble the interactions observed for other ligands. The heme proximal region comprises the intermolecular interface in AROM, and also the putative interaction surface of its redox partner cytochrome P450 reductase. Unreported previously, the proximal region is characterized by a large surface cavity, unlike most known P450's. Using five best X-ray data sets from androstenedione and testosterone complexes of AROM, we now unequivocally show the presence of an unexplained ligand electron density inside the proximal cavity. The density is interpreted as ordered five ethylene glycol units of polyethylene glycols used as a solvent for steroids and also in crystallization. Interestingly, polyethylene glycol exhibits weak inhibition of AROM enzyme activity in a time dependent manner. Besides its critical role in the redox partner coupling and electron transfer process, the proximal cavity possibly serves as the interaction site for other molecules that may have regulatory effects on AROM activity. In addition, the new data also reveal a previously unidentified water channel linking the active site to the lipid interface. The channel could be the predicted passage for water molecules involved in catalysis.
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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.