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Manumycin natural products were found to target the E3 ligase UBR7 and engage in molecular glue interactions with p53, leading to the activation of p53 and cell death.
A structural and biochemical study of bacterial β-barrel assembly machinery component BamA with transport substrate RcsF shows an inward-open conformation with RcsF trapped inside the β-barrel lumen and suggests a push–pull substrate export mechanism.
Single-molecule and super-resolution approaches define a monomer–dimer equilibrium of µ-opioid receptors and show that receptors form agonist-induced dimers coincident with β-arrestin2 binding to receptors.
The iPROBE platform accelerates the design and optimization of engineered biosynthetic pathways using a combination of cell-free protein synthesis, in vitro pathway assembly and a scoring system to identify high-performing combinations.
A 19F-NMR-based method monitoring the conformational dynamics of the glutamate transporter GltPh identified one inward- and two outward-facing states, including one unanticipated outward-facing state that was characterized by cryo-EM.
Activity-based protein profiling (ABPP) was used to identify and optimize bioactive, selective pharmacological enzyme activators of the serine hydrolase LYPLAL1, which improved the metabolic defects of diet-induced obese mice.
A combination of tRNA sequencing and mass spectrometry was developed to profile tRNA modification enabling identification of a new modification acacp3U and the presence of cytosine-to-pseudouracil RNA editing in Vibrio cholerae.
A negative allosteric modulator of the G-protein-coupled receptor β2-adrenergic receptor binds to a membrane-facing surface adjacent to a molecular switch for receptor activation, and its binding disrupts a water-mediated polar network stabilizing an inactive switch conformation.
Using a new method to generate site-specific monoubiquitinated proteins, the authors find monoubiquitination has a site-specific effect on protein stability and proteasomal processing.
Cellular glycosylation facilitates molecular recognition of cells and biomolecules. A two-step N-glycan editing method enables selective glycoform ‘deletion’ and ‘insertion’ of new glycans, which can be used to probe their biological functions.
Rather than a typical S-adenosylmethionine-dependent alkyltransferase, the installation of the N-alkylamine linker in several nucleoside antibiotics is catalyzed via γ-replacement by a pyridoxal-5′-phosphate-dependent aminobutyryltransferase.
A highly selective covalent peptide inhibitor of the peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is used to show that Pin1 cooperates with mutant KRAS to promote pancreatic ductal adenocarcinoma (PDAC) transformation.
Comprehensive informatic, structural and biochemical characterization of the GH128 family defines subgroups of glycoside hydrolase enzymes with unique recognition and cleavage mechanisms for 1,3-beta-glucan polysaccharide substrates.
Prostaglandins PGE1 and PGA1 have neuroprotective effects by enhancing the transcriptional activity of Nurr1 by directly binding to its ligand-binding domain and upregulating their target genes implicated in Parkinson’s disease.
Imaging studies revealed that m6A-binding YTHDF proteins promoted phase separation of core proteins of stress granules by reducing the critical size and activation energy barrier, thus promoting the formation of stress granules in cells.
Engineering of yeast transcription factors and design of hybrid DNA promoter elements have resulted in a toolkit for tunable and orthogonal regulation of gene expression in Arabidopsis thaliana and Nicotianabenthamiana plants.
Biosensors of guanine exchange factors (GEFs) and red-shifted GTPase biosensors are used to visualize GEF and GTPase activities in the same cells and enable correlation analysis to reveal which GEF–GTPase interactions regulate cell movement.
Evolution of a group of plant cellulose synthase-like enzymes into specialized glycosyltransferases in the endoplasmic reticulum membrane confers the ability to glucuronidate triterpenoid saponins and other specialized metabolites.
Identification of an improved glucose-6-phosphate dehydrogenase (G6PD) inhibitor G6PDi-1 blocks G6PD activity more robustly than the widely cited antagonist DHEA. G6PDi-1 treatment blocks T cell cytokine production and neutrophil oxidative burst.
Structures of 5-lipoxygenase (5-LOX) reveal that NDGA disturbs regions that shield the active site while AKBA binds an allosteric site. NDGA inhibits 5-LOX activity using its redox-active function, while AKBA changes the enzyme’s regiospecificity