Structural modification of a series of dual LXRα/β agonists led to the identification of a new class of LXRβ partial agonists. An X-ray co-crystal structure shows that a representative member of this series, pyrrole 5, binds to LXRβ with a reversed orientation compared to 1.
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http://dx.doi.org/10.1016/j.bmcl.2012.02.028 | DOI Listing |
Protein Sci
February 2025
Department of Physics, University of Washington, Seattle, Washington, USA.
Proteins' flexibility is a feature in communicating changes in cell signaling instigated by binding with secondary messengers, such as calcium ions, associated with the coordination of muscle contraction, neurotransmitter release, and gene expression. When binding with the disordered parts of a protein, calcium ions must balance their charge states with the shape of calcium-binding proteins and their versatile pool of partners depending on the circumstances they transmit. Accurately determining the ionic charges of those ions is essential for understanding their role in such processes.
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January 2025
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea; Elicure, 12, Gyeongyeol-ro 17 beon-gil, Seo-gu, Gwangju, Republic of Korea. Electronic address:
This study aimed to profile metabolites from five Trichoderma strains and assess their cytotoxic and pharmacological activities, particularly targeting oral squamous cell carcinoma (OSCC). UHPLC-TOF-MS analysis revealed the presence of 25 compounds, including heptelidic acid, viridiol isomers, and sorbicillinol from the different Trichoderma extracts. Pharmacokinetic analysis showed moderate permeability and low interaction with P-glycoprotein, suggesting good drug absorption with minimal interference in cellular uptake.
View Article and Find Full Text PDFBiosci Biotechnol Biochem
January 2025
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
Protein kinase C (PKC) is a family of serine/threonine kinases, and PKC ligands have the potential to be therapeutic seeds for cancer, Alzheimer's disease, and human immunodeficiency virus infection. However, in addition to desired therapeutic effects, most PKC ligands also exhibit undesirable pro-inflammatory effects. The discovery of new scaffolds for PKC ligands is important for developing less inflammatory PKC ligands, such as bryostatins.
View Article and Find Full Text PDFLancet Neurol
February 2025
Department of Neurosciences, and Leuven Brain Institute, University of Leuven, Leuven, Belgium; Laboratory of Neurobiology, Center for Brain & Disease Research, VIB, Leuven, Belgium. Electronic address:
Autosomal dominant mutations in the gene encoding the DNA and RNA binding protein FUS are a cause of amyotrophic lateral sclerosis (ALS), and about 0·3-0·9% of patients with ALS are FUS mutation carriers. FUS-mutation-associated ALS (FUS-ALS) is characterised by early onset and rapid progression, compared with other forms of ALS. However, different pathogenic mutations in FUS can result in markedly different age at symptom onset and rate of disease progression.
View Article and Find Full Text PDFStructure
January 2025
Department of Hepatobiliary Surgery, Innovative Institute of Tumor Immunity and Medicine (ITIM), Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. Electronic address:
NSUN6 preferentially catalyzes the methylation of cytosine nucleotides in mRNA substrates, which enhances transcription. Dysregulation of NSUN6 catalysis drives the oncogenesis of certain cancers. In this study, we determined the crystal structure of human NSUN6 in complex with its S-adenosyl-L-methionine analog and a bound NECT-2 3'-UTR RNA substrate at 2.
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