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A hydrophobic tagging method is used to develop a selective degrader for the chromatin regulator EZH2, which inhibits proliferation of triple-negative breast cancer cell lines in vitro and in vivo.
Single-particle tracking and mathematical modeling methods reveal the searching mechanism of CTCF for its cognate sites on DNA. An RNA-binding region in CTCF mediates its trapping in small zones and increases its target search efficiency.
A computational approach for designing GPCRs with new signaling functions including allosteric signaling properties yielded D2 receptor variants with predictable G-protein signaling responses, some with enhanced potency and responses to dopamine.
3D printing agarose hydrogels embedded with Bacillus subtilis spores produce custom-shaped materials that are resistant to environmental stresses, while the bacteria maintain the ability to germinate on the surface and respond to stimuli.
The cellular stability of an oncogenic factor, AIMP2-DX2, is increased via association with HSP70. Interference with this interaction by a small-molecule compound promotes ubiquitin-mediated degradation of AIMP2-DX2 and reduces cancer cell growth.
A potent inhibitor of the MRSA virulence regulator, GraR, reverses methicillin resistance, inhibits biofilm formation, limits bacterial survival in macrophages and attenuates virulence in vitro, synergizing with cationic antimicrobial peptides.
Sulfur-triazole exchange (SuTEx) chemistry is a tunable platform for covalent chemoproteomic probes that selectively target tyrosines, used to identify residues with enhanced nucleophilicity and monitor activation of phosphotyrosine sites.
Redesign of a glucose dehydrogenase to use nicotinamide mononucleotide (NMN+) instead of NAD(P)+ enables the development of a noncanonical cofactor system that can be used to support redox chemistries both in vitro and in Escherichia coli.
Two bioinformatic tools, BiG-SCAPE and CORASON, enable sequence similarity network and phylogenetic analysis of gene clusters and their families across hundreds of strains and in large datasets, leading to the discovery of new natural products.
Actin cytoskeletal structures are essential for many cellular processes, and cofilin is a key protein for the assembly of these highly dynamic structures. A new cofilin construct enables precise optogenetic control of actin assembly in live cells.
The last step of archaeosine biosynthesis was found to involve two enzymes, the previously known ArcS with lysine transfer activity and a novel identified radical SAM enzyme named RaSEA.
The regulation of brain iron homeostasis, previously thought to be cell autonomous and modulated by local factors in the interstitial fluid, is reported by Wang et al. to be strongly influenced by axonal transport of iron in an activity-dependent and unidirectional manner between functionally associated regions. The supply of iron from the ventral hippocampus to the middle prefrontal cortex subserved an anxiolytic phenotype and mediated the neuropharmacological actions of diazepam and lithium chloride in rodent models.
Euryarchaeal ArcS alone cannot produce G+-containing tRNA but works as a lysine transferase to produce a lysine adduct intermediate, which finally forms G+-containing tRNA in the presence of a newly identified SAM enzyme, RaSEA.
A mitochondrial-targeted acyl protein thioesterase inhibitor enables the identification of ABHD10 as a mitochondrial S-depalmitoylase that acts on the nucleophilic active site residue of peroxiredoxin-5 to modulate its antioxidant capacity.
Z-lock is introduced as a new method to control protein activity with light. It relies on a steric block placed over important regions of the target protein that can be released reversibly. Z-lock was applied to regulate cofilin and αTAT activity.
Microbiota-derived butyrate acylation of the key Salmonella enterica transcriptional regulator HilA attenuates virulence of the bacteria, blocking invasion of epithelial cells in vitro and dissemination in vivo.