ArticleThe Journal of biological chemistry2012
Deciphering modern glucocorticoid cross-pharmacology using ancestral corticosteroid receptors.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Hot melt extruded Kyungohkgo attenuates skeletal muscle atrophy by downregulating the FOXO3a/MuRF-1/atrogin-1 axis.Scientific reports · 2026Article
- Review
- Identification of an Evolutionarily Conserved Allosteric Network in Steroid Receptors.Journal of chemical information and modeling · 2023Article
- Glucocorticoid receptor condensates link DNA-dependent receptor dimerization and transcriptional transactivation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Disruption of a key ligand-H-bond network drives dissociative properties in vamorolone for Duchenne muscular dystrophy treatment.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Experimental Glucocorticoid Receptor Agonists for the Treatment of Asthma: A Systematic Review.Journal of experimental pharmacology · 2020Review
- First High-Resolution Crystal Structures of the Glucocorticoid Receptor Ligand-Binding Domain-Peroxisome Proliferator-ActivatedMolecular pharmacology · 2019Article
- Structural Analysis of the Glucocorticoid Receptor Ligand-Binding Domain in Complex with Triamcinolone Acetonide and a Fragment of the Atypical Coregulator, Small Heterodimer Partner.Molecular pharmacology · 2017Article
- Chiral Alkyl Halides: Underexplored Motifs in Medicine.Marine drugs · 2016Review
- Functional Divergence of the Nuclear Receptor NR2C1 as a Modulator of Pluripotentiality During Hominid Evolution.Genetics · 2016Article
- A Natural Mutation in Helix 5 of the Ligand Binding Domain of Glucocorticoid Receptor Enhances Receptor-Ligand Interaction.PloS one · 2016Article
- Biochemistry and evolutionary biology: two disciplines that need each other?Journal of biosciences · 2014Article
- Role of Per1 and the mineralocorticoid receptor in the coordinate regulation of αENaC in renal cortical collecting duct cells.Frontiers in physiology · 2013Article
- Article
- Non-genomic effect of glucocorticoids on cardiovascular system.Pflugers Archiv : European journal of physiology · 2012Review
- A phylogenetic analysis of normal modes evolution in enzymes and its relationship to enzyme function.Journal of molecular biology · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Steroid receptors (SRs) are the largest family of metazoan transcription factors and control genes involved in development, endocrine signaling, reproduction, immunity, and cancer. The entire hormone receptor system is driven by a molecular switch triggered by the binding of small lipophilic ligands. This makes the SRs ideal pharmaceutical targets, yet even the best clinically approved synthetic steroidal agonists are prone to cross-reactivity and off-target pharmacology. The mechanism underlying this promiscuity is derived from the fact that SRs share common structural features derived from their evolutionary relationship. More often than not, rational attempts to probe SR drug selectivity via mutagenesis fail even when high quality structural and functional data are available due to the fact that important mutations often result in nonfunctional receptors. This highlights the fact that SRs suffer from instability, preventing in-depth mutational analysis and hampering crystallization of key receptor-ligand complexes. We have taken a unique approach to address this problem by using a resurrected ancestral protein to determine the structure of a previously intractable complex and identified the structural mechanisms that confer activation and selectivity for a widely used glucocorticoid, mometasone furoate. Moreover, we have identified a single residue located outside of the ligand-binding pocket that controls mometasone furoate antagonism versus agonism in the human mineralocorticoid receptor.
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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.