Publications by authors named "R F Keyes"
Article Synopsis
- * The study identified TRIM33 as the only bromodomain protein that binds to histone Kla peptides, which suggests that it may help inhibit inflammatory gene expression during macrophage activation.
- * Using various biophysical techniques, researchers confirmed that TRIM33 has a strong binding affinity for both Kla and acetylated lysine, with a specific glutamic acid residue in its binding pocket crucial for recognizing Kla, highlighting TRIM33's potential role in macrophage polarization and
Article Synopsis
- AAR positive allosteric modulators (PAMs) enhance the effects of AAR agonists by binding at a lipid-exposed site, without increasing their potency due to the presence of antagonism.
- Researchers modified the chemical structure of PAMs by introducing various substitutions and extensions to improve their allosteric binding to both human and mouse AARs.
- The mechanism behind this improvement involves a flexible chain that interacts with the lipid environment, indicating a novel way of stabilizing the PAM binding through electrostatic interactions with phospholipid head groups.
This study describes the localization and computational prediction of a binding site for the A adenosine receptor (AAR) positive allosteric modulator 2-cyclohexyl-1-imidazo[4,5-c]quinolin-4-(3,4-dichlorophenyl)amine (LUF6000). The work reveals an extrahelical lipid-facing binding pocket disparate from the orthosteric binding site that encompasses transmembrane domain (TMD) 1, TMD7, and Helix (H) 8, which was predicted by molecular modeling and validated by mutagenesis. According to the model, the nearly planar 1-imidazo[4,5-c]quinolinamine ring system lies parallel to the transmembrane segments, inserted into an aromatic cage formed by π-π stacking interactions with the side chains of Y284 in TMD7 and Y293 in H8 and by π-NH bonding between Y284 and the exocyclic amine.
View Article and Find Full Text PDFTriphenylphosphonium (TPP) compounds like mito-metformin (MMe) target cancer cells by exploiting their hyperpolarized mitochondrial membrane potential. Here, we present a protocol for synthesizing TPP analogs with selectivity for mammalian cancer cells, reduced toxicity, and quantifiability using fluorine-19 nuclear magnetic resonance (F-NMR). We describe steps for treating mammalian cells with mitochondria-targeted compounds, treating and preparing mouse tissue with these compounds, and F-NMR detection of MMe analogs in cells and tissue.
View Article and Find Full Text PDFBackground: Oxidative stress contributes to thrombosis in atherosclerosis, inflammation, infection, aging, and malignancy. Oxidant-induced cysteine modifications, including sulfenylation, can act as a redox-sensitive switch that controls protein function. Protein disulfide isomerase (PDI) is a prothrombotic enzyme with exquisitely redox-sensitive active-site cysteines.
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