Articles

A gradient of cAMP in developing hippocampal neurons that is important for axon elongation is shaped by spatial differences in phosphodiesterase localization and is maintained by AKAP-anchored PKA, as revealed by using FRET-based biosensors.

Reconstitution experiments using substrates prepared by chemoenzymatic synthesis demonstrate that three LCP family proteins catalyze the ligation of wall teichoic acids to peptidoglycan in the biosynthesis of the Staphylococcus aureus cell wall.

The Ni(ii) affinity of Ni(ii) sensor InrS is attuned to buffered Ni(ii) concentrations, explaining why these two parameters co-vary for different metals over many orders of magnitude.

Spectroscopic studies of allosteric activation of Aurora A kinase using a site-specific infrared probe combined with FRET analysis and molecular dynamics simulations reveals a water-mediated hydrogen bond network in the active site that regulates Aurora A activity.

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 GABA_B 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.

Orthogonal cholesterol sensors that are useful for imaging cholesterol in the plasma membrane leaflets reveal an asymmetry in which a high outer leaflet concentration is important for signaling processes and is potentially actively maintained.

The ‘CoINPocket’ approach identifies pharmacological similarities between G protein–coupled receptors. On the basis of predicted pharmacological similarity to a few phylogenetically unrelated receptors, the approach identified surrogate ligands for the orphan receptor GPR37L1.

A high-throughput screen identifies inhibitors of the M. tuberculosis dormancy regulation system, DosRST, including compounds that inhibit autophosphorylation of the DosS and DosT sensor kinases and those that inhibit the catalytic heme of these kinases.

Structural and functional characterization of an aromatic prenyltransferase reveals a unique spacious hydrophobic pocket with conformational fluctuation and multiple acceptor binding sites that endow it with uncommon enzymatic promiscuity.