Farnesoid X receptor (FXR) belongs to the nuclear receptor superfamily. It is highly related to the formation of metabolic syndrome and the glucose homeostasis, and therefore represents an important drug target against metabolic diseases and diabetes. In recent years, great progress has been made in the agonists, antagonists, and crystal structures of FXR. The diverse FXR ligands and their structure-activity relationship are reviewed in this article. The advances in the crystal structures of FXR in complex with different ligands are also introduced.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Electron transfer in polysaccharide monooxygenase catalysis.
Proc Natl Acad Sci U S A
January 2025
California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720.
Polysaccharide monooxygenase (PMO) catalysis involves the chemically difficult hydroxylation of unactivated C-H bonds in carbohydrates. The reaction requires reducing equivalents and will utilize either oxygen or hydrogen peroxide as a cosubstrate. Two key mechanistic questions are addressed here: 1) How does the enzyme regulate the timely and tightly controlled electron delivery to the mononuclear copper active site, especially when bound substrate occludes the active site? and 2) How does this electron delivery differ when utilizing oxygen or hydrogen peroxide as a cosubstrate? Using a computational approach, potential paths of electron transfer (ET) to the active site copper ion were identified in a representative AA9 family PMO from (PMO9E).
View Article and Find Full Text PDFEvaluation of Larger Side-Group Functionalities and the Side/End-Group Interplay in Ritonavir-Like Inhibitors of CYP3A4.
Chem Biol Drug Des
January 2025
Department of Molecular Biology and Biochemistry, University of California, Irvine, California, USA.
A new series of 13 ritonavir-like inhibitors of human drug-metabolizing CYP3A4 was rationally designed to study the R side-group and R end-group interplay when the R side-group is represented by phenyl. Spectral, functional, and structural characterization showed no improvement in the binding affinity and inhibitory potency of R/R-phenyl inhibitors upon elongation and/or fluorination of R-Boc (tert-butyloxycarbonyl) or its replacement with benzenesulfonyl. When R is pyridine, the impact of R-phenyl-to-indole/naphthalene substitution was multidirectional and highly dependent on side-group stereo configuration.
View Article and Find Full Text PDFIsolation and structure of broad SIV-neutralizing antibodies reveal a proximal helical MPER epitope recognized by a rhesus multi-donor class.
Cell Rep
January 2025
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
The membrane-proximal external region (MPER) of the HIV-1 envelope is a target for broadly neutralizing antibodies (bnAbs), and vaccine-elicited MPER-directed antibodies have recently been reported from a human clinical trial. In this study, we sought to identify MPER-directed nAbs in simian immunodeficiency virus (SIV)-infected rhesus macaques. We isolated four lineages of SIV MPER-directed nAbs from two SIV-infected macaques.
View Article and Find Full Text PDFLigand-Induced Intramolecular Cuprophilic and Argentophilic Interactions in Bimetallic Cu(I) and Ag(I) Phosphine Complexes and the Assessment of Their Antityrosinase and Antibacterial Effects.
Inorg Chem
January 2025
Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, 3012 Bern, Switzerland.
Binuclear silver(I) and copper(I) complexes, and , with bridging diphenylphosphine ligands were prepared. In , the silver(I) center is located inside a trigonal plane composed of three phosphorus donors from three separate and bridging dppm ligands. The fourth coordination site is filled with neighboring silver(I) ions.
View Article and Find Full Text PDFUnearthing the emerging properties at buried oxide heterointerfaces: the γ-AlO/SrTiO heterostructure.
Mater Horiz
January 2025
Department of Energy Conversion and Storage, Technical University of Denmark, Fysikvej, Building 310, 2800 Kgs. Lyngby, Denmark.
The symmetry breaking that is formed when oxide layers are combined epitaxially to form heterostructures has led to the emergence of new functionalities beyond those observed in the individual parent materials. SrTiO-based heterostructures have played a central role in expanding the range of functional properties arising at the heterointerface and elucidating their mechanistic origin. The heterostructure formed by the epitaxial combination of spinel γ-AlO and perovskite SrTiO constitutes a striking example with features distinct from perovskite/perovskite counterparts such as the archetypical LaAlO/SrTiO heterostructure.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!