Results 31 to 40 of about 37,458 (256)
AI-Driven Design of Miniproteins as Potential Allosteric Modulators
PharmaceuticalsAllosteric modulation has emerged as a powerful strategy for achieving superior selectivity and safety in drug discovery and protein function regulation.
Xin Liu +4 more
doaj +1 more source
FEBS Letters, EarlyView.Biomolecular condensates formed by fused in sarcoma (FUS) are dissolved by high ATP concentrations yet persist in cells. Using a reconstituted system, we demonstrate that valosin‐containing protein (VCP), an AAA+ ATPase, counteracts ATP‐driven dissolution of FUS condensates through its D2 ATPase activity.
Hitomi Kimura +2 more
wiley +1 more source
Biased Signaling and Allosteric Modulation at the FSHR [PDF]
Frontiers in Endocrinology, 2019 Knowledge on G protein-coupled receptor (GPCRs) structure and mechanism of activation has profoundly evolved over the past years. The way drugs targeting this family of receptors are discovered and used has also changed. Ligands appear to bind a growing number of GPCRs in a competitive or allosteric manner to elicit balanced signaling or biased ...
Landomiel, Flavie +10 more
openaire +5 more sources
Development of allosteric modulators of GPCRs for treatment of CNS disorders
Neurobiology of Disease, 2014 The discovery of allosteric modulators of G protein-coupled receptors (GPCRs) provides a promising new strategy with potential for developing novel treatments for a variety of central nervous system (CNS) disorders.
Hilary Highfield Nickols +1 more
doaj +1 more source
eLife, 2020 Pentameric ligand-gated ion channels (pLGICs) or Cys-loop receptors are involved in fast synaptic signaling in the nervous system. Allosteric modulators bind to sites that are remote from the neurotransmitter binding site, but modify coupling of ligand ...
Marijke Brams +12 more
doaj +1 more source
Allosteric crosstalk in modular proteins: Function fine-tuning and drug design
Computational and Structural Biotechnology Journal, 2023 Modular proteins are regulatory proteins that carry out more than one function. These proteins upregulate or downregulate a biochemical cascade to establish homeostasis in cells.
Suman Abhishek +4 more
doaj +1 more source
pH‐mediated activation of the lysosomal arginine sensor SLC38A9
FEBS Letters, EarlyView.Cells monitor nutrient levels via the lysosomal transporter SLC38A9 to activate the mechanistic target of rapamycin complex 1 (mTORC1). This study reveals that SLC38A9 function is regulated by pH. We identified histidine 544 as a critical pH sensor that undergoes conformational changes to control amino acid efflux from lysosomes; therefore, it ...
Xuelang Mu, Ampon Sae Her, Tamir Gonen
wiley +1 more source
Phosphoinositides and inositol phosphates as molecular glues
FEBS Letters, EarlyView.Inositol phosphates (IPs) and phosphoinositides (PIPs) regulate diverse eukaryotic processes. Beyond recruiting signaling proteins or acting as structural cofactors, recent studies suggest they mediate protein–protein interactions as natural molecular glues.
Aleshia Seaton‐Terry +9 more
wiley +1 more source
Allosteric Modulators: A Side Door [PDF]
Journal of Medicinal Chemistry, 2015 Allosteric modulators of the cannabinoid CB1 receptor were first discovered in 2005. Since then, although both negative and positive allosteric modulators have been uncovered, many questions remain about their site(s) of action, as well as the basis of their signaling.
openaire +2 more sources
Allosteric modulation of DNA by small molecules [PDF]
Proceedings of the National Academy of Sciences, 2009 Many human diseases are caused by dysregulated gene expression. The oversupply of transcription factors may be required for the growth and metastatic behavior of human cancers. Cell permeable small molecules that can be programmed to disrupt transcription factor-DNA interfaces could silence aberrant gene expression pathways.
Chenoweth, David M., Dervan, Peter B.
openaire +3 more sources