The long-range side-chain repulsion between the (1R,2R,3R,5R)-2-amino-6,6-dimethyl-bicyclo[3.1.1]-heptane-3-carboxylic acid (trans-ABHC) residues stabilize the H12 helix in beta-peptide oligomers.
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http://dx.doi.org/10.1039/b812114a | DOI Listing |
Blood
October 2024
Precision Medicine Center, Beijing Lu Daopei Institute of Hematology, Beijing, China.
J Chem Phys
March 2024
Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Nuclear receptors regulate transcriptional programs in response to the binding of natural and synthetic ligands. These ligands modulate the receptor by inducing dynamic changes in the ligand binding domain that shift the C-terminal helix (H12) between active and inactive conformations. Despite decades of study, many questions persist regarding the nature of the inactive state and how ligands shift receptors between different states.
View Article and Find Full Text PDFEnviron Sci Technol
February 2024
Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, School of Environment and Health, Jianghan University, Wuhan 430056, China.
Over the past few decades, extensive research has indicated that exposure to bisphenol A (BPA) increases the health risks in humans. Toxicological studies have demonstrated that BPA can bind to the androgen receptor (AR), resulting in endocrine-disrupting effects. In recent investigations, many alternatives to BPA have been detected in various environmental media as major pollutants.
View Article and Find Full Text PDFJ Clin Invest
January 2024
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Physiologic activation of estrogen receptor α (ERα) is mediated by estradiol (E2) binding in the ligand-binding pocket of the receptor, repositioning helix 12 (H12) to facilitate binding of coactivator proteins in the unoccupied coactivator binding groove. In breast cancer, activation of ERα is often observed through point mutations that lead to the same H12 repositioning in the absence of E2. Through expanded genetic sequencing of breast cancer patients, we identified a collection of mutations located far from H12 but nonetheless capable of promoting E2-independent transcription and breast cancer cell growth.
View Article and Find Full Text PDFACS Chem Biol
May 2023
The Institute for Photonics and Advanced Sensing and School of Biological Sciences, The University of Adelaide, Adelaide, South Australia 5005, Australia.
Inverse agonists of peroxisome proliferator activated receptor γ (PPARγ) have emerged as safer alternatives to full agonists for their reduced side effects while still maintaining impressive insulin-sensitizing properties. To shed light on their molecular mechanism, we characterized the interaction of the PPARγ ligand binding domain with SR10221. X-ray crystallography revealed a novel binding mode of SR10221 in the presence of a transcriptionally repressing corepressor peptide, resulting in much greater destabilization of the activation helix, H12, than without corepressor peptide.
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