Structural insights into the molecular mechanism of vitamin D receptor activation by lithocholic acid involving a new mode of ligand recognition. | LitMetric
Department of Integrative Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de Santé et de Recherche Médicale (INSERM) U964, Centre National de Recherche Scientifique (CNRS) UMR 7104, Université de Strasbourg, 67404 Illkirch, France.
Published: June 2014
AI Article Synopsis
Article Abstract
The vitamin D receptor (VDR), an endocrine nuclear receptor for 1α,25-dihydroxyvitamin D3, acts also as a bile acid sensor by binding lithocholic acid (LCA). The crystal structure of the zebrafish VDR ligand binding domain in complex with LCA and the SRC-2 coactivator peptide reveals the binding of two LCA molecules by VDR. One LCA binds to the canonical ligand-binding pocket, and the second one, which is not fully buried, is anchored to a site located on the VDR surface. Despite the low affinity of the alternative site, the binding of the second molecule promotes stabilization of the active receptor conformation. Biological activity assays, structural analysis, and molecular dynamics simulations indicate that the recognition of two ligand molecules is crucial for VDR agonism by LCA. The unique binding mode of LCA provides clues for the development of new chemical compounds that target alternative binding sites for therapeutic applications.
Background: Melanoma is an aggressive skin tumor with limited therapeutic options due to rapid proliferation, early metastasis, and poor prognosis. Baicalin (BA), a natural flavonoid, shows promise in inducing ferroptosis and apoptosis but faces challenges of poor solubility and bioavailability. To address these issues, we developed a multifunctional drug delivery system: manganese-doped ZIF-8 nanoparticles (ZIF(Mn)) loaded with BA and modified with folic acid (FA) and polyethylene glycol (PEG).
This editorial aims to elucidate the intricate relationship between vitamin D and viral pathogenesis. It explores the anticipated role of vitamin D as a modulator in the immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viral pathogens. The editorial comments are based on the review article by Engin .
As a novel organophosphate ester (NOPE), tris(2,4-di-butylphenyl) phosphate (TDtBPP) has attracted significant attention due to its unexpectedly high detection in natural environments. However, the ecological toxic effects of environmentally relevant concentrations of TDtBPP in organisms remain entirely unknown. In this study, 1 month old zebrafish were exposed to 0, 50, 500, or 5000 ng/L TDtBPP for 150 days, and the reproductive toxicity in male fish was evaluated.
Background: Vitamin D leads to the activation of macrophages and limitation of intracellular growth of Mycobacterium tuberculosis. Vitamin D receptor (VDR) gene polymorphisms can facilitate the development of tuberculosis (TB). Therefore, the present study aimed to investigate the effect of vitamin D supplementation on response to treatment in patients with pulmonary TB for different VDR polymorphisms.
