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H3K27me3 binding to the EED pocket of the Polycomb repressive complex 2 (PRC2) is required to activate PRC2. An allosteric small-molecule inhibitor of PRC2 was identified that binds to the EED pocket and blocks PRC2 methyltransferase activity in cells.
A pyrrolidine-based small-molecule inhibitor competes with H3K27me3 for binding to EED leading to inactivation of PRC2 and global reduction in H3K27me3 levels.
Optimizing the signal-to-noise ratio in time-resolved FRET through generation of agonist-responsive cell-surface receptor biosensors, including GABAB receptors and EGFR, which are useful for monitoring conformational changes associated with receptor activation.
SUV4-20 members mediate the di- and trimethylation of lysine 20 on histone H4. A chemical screen led to the identification of A-196 as a potent and selective inhibitor of SUV4-20 that decreases H4K20 methylation and alters DNA damage response.
The use of the T-REX redox targeting platform to identify proteins that react with lipid-derived electrophiles in cells and zebrafish reveals that hydroxynoneal (HNE)-mediated modification of Akt3 C119 decreases Akt3 activity.
Discovery and characterization of two Brønsted acid enzymes from quinolone alkaloid biosynthesis provides new biocatalytic approaches for the challenging but synthetically useful cationic rearrangement of epoxides.
The use of an alkyne–adenosine analog enables the labeling and detection of ADP-ribosylated proteins under oxidative stress and reveals a role of Hras ADP-ribosylation to regulate its signaling.
In vitro selection of RNA libraries constructed by randomization of RNA structural scaffolds from known ribozymes and riboswitches led to the identification of aptamers that were readily translated into functional biosensors in cells.
Crystallographic snapshots illustrate the catalytic cycle and illuminate the mechanism by which the enzyme Pdx1 shuttles intermediates between lysine residues in its two active sites during the biosynthesis of pyridoxal 5′-phosphate.
A synthetic biology approach involving engineered mammalian cell consortia converts analog sensing of fragrance molecules into control of reporter-gene expression and amplifies the signal, thus enabling the digitization of molecular signals for cybernetic devices.
SHAPE and DMS in vitro chemical probing analysis reveals the secondary structure of the RepA long noncoding RNA, and UV-cross-linking and RNA modeling analyses produce a 3D model of RepA depicting phylogenetically conserved domains.
Structural characterization of the bifunctional enzyme linalool dehydratase isomerase and exploration of its substrate scope demonstrate its potential for catalyzing desirable transformations of various tertiary alcohols.