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Cytosolic 2-Cys peroxiredoxins can enable, rather than compete with, rapid thiol oxidation by relaying H2O2-derived oxidizing equivalents to other proteins, suggesting a broadened role for peroxiredoxins as sensors and transmitters of H2O2 signals.
A selective small-molecule degrader of CDK9 was generated by conjugating an imide to SNS-032, a promiscuous ATP-site-directed CDK binder. The pharmacological consequences of CDK9 degradation versus inhibition were compared.
A modular protein expression system enables the structural and functional characterization of human glycosyltransferases, glycoside hydrolases and other carbohydrate-modifying enzymes.
A potent inhibitor of the conditionally essential mitochondrial phosphate carrier protein Mir1 in the fungi Candida albicans diminishes mitochondrial oxygen consumption and causes dramatic changes in concentrations of citrate and succinate.
D2 dopamine receptor ligands biased for b-arrestin recruitment were developed based on a receptor homology model that identified conserved ligand contacts within the TM5 and EL2 regions as important for biased signaling.
Two complementary coiled-coil peptides and a bacterial microcompartment shell protein are combined to construct cytoscaffolds within Escherichia coli cells. Targeting enzymes to the cytoplasmic scaffold results in colocalization and improved metabolic flux.
A selective inhibitor of the deubiquitinase USP7 binds an allosteric site to inhibit its MDM2-stabilizing activity, resulting in stabilization of p53 and p21, which confers hypersensitivity to cancer cells for killing by the compound.
Selections with a phage-displayed antibody library against an existing protein–small-molecule complex enabled the generation of antibody-based chemically induced dimerizers (AbCIDs) with the properties necessary for use in regulating cell therapies.
Protein O-fucosyltransferase 1 (Pofut1) regulates Notch activity by adding O-fucose residues to its extracellular domain. Fucose analogs were identified that inhibited Delta-mediated Notch binding and activation but spared Jagged1-mediated signaling.
Direct conversion of 5-fdC into dC by C–C bond breakage is revealed by metabolic tracing studies through incorporation of synthetic stable isotope- and (R)-2′-fluorine-labeled dC and fdC derivatives into the genome of cultured mammalian cells.
High-throughput screening identified potent small-molecule inhibitors of the endosomal Toll-like receptor TLR8 that stabilize the preformed TLR8 dimer in its resting state by binding to a unique site on the inactive dimer interface.
Biosynthesis of the antibiotic sulfazecin involves N-sulfonation in trans of the tripeptide intermediate before synthesis of the β-lactam ring by a noncanonical thioesterase domain, demonstrating a new enzymatic route to the azetidinone moiety.
A comprehensive characterization of peptide ligase specificity using proteome-derived peptide libraries enables the identification of 72 new subtiligases and their application to site-specific bioconjugation and sequencing of the cellular N terminome.
Strains of Escherichia coli, each expressing a subset of the 34 translation machinery proteins, are grown in synthetic microbial consortia to enable the efficient isolation of the full machinery from a single culturing, lysis, and purification procedure.
Engineering of nonimmune cells with a cell-contact sensor and antigen recognition domains enables cell-contact-dependent sensor cell signaling and effector molecule production directed to attack target cells, providing an alternative strategy to chimeric antigen receptor T-cell (CAR-T) technology.
A multistage tandem mass spectrometry approach enables the application of native proteomics to characterize intact endogenous protein complexes in discovery mode, including covalent modifications as well as noncovalently bound cofactors and ligands.
Mass-spectrometry-based metabolomics analysis of oligodendrocyte differentiation led to the identification of an endogenous metabolite, taurine, that enhanced the process of drug-induced OPC differentiation.
In organohalide-respiring bacteria, reductive dehalogenases cleave carbon–halogen bonds using cobamide prosthetic groups. Desulfitobacterium hafniense uses an unprecedented cobamide variant, which includes unsubstituted purine, for this function.
Ultrasensitive imaging of lanthanide chelates is achieved by integrating transreflected illumination, luminescence resonance energy transfer, and time-resolved microscopy.
Synthetic beta cells were fabricated through 'vesicles-in-vesicle' liposomal superstructures equipped with glucose-sensing and membrane-fusion machinery, thus enabling sensing of graded glucose levels and secretion of insulin via fusion processes.