Articles in 2016

Structural, enzymatic and cellular target engagement studies reveal the mechanism of action by N-hydroxyurea small molecule inhibitors of the DNA repair enzyme, human flap endonuclease-1 (FEN1) that prevent cleavage of DNA flaps in cancer cells.

A single-molecule approach demonstrates that TALEs scan DNA using a unique ‘zip-line’ mechanism wherein the TALEs move without rotating along the DNA helix, yet the DNA remains threaded through the loosely wrapped TALE.

A cyclobutane compound competitively inhibits the activity of androgen receptors (AR) containing antiandrogen-resistant mutations through stabilization of the receptor in an apo-like conformation and preventing AR nuclear entry.

The modification of Cdc42 with a FRET binding antenna (GDI.Cdc42 FLARE) enables detection of Cdc42 binding to guanine-nucleotide dissociation inhibitor (GDI) and Cdc42 activation with improved spatial-temporal resolution during cellular protrusion and retraction.

Nemamides are hybrid polyketide–nonribosomal peptide natural products that were identified by metabolomics profiling in Caenorhabditis elegans and are involved in the organism's survival response to nutrient-deficient conditions.

The application of a potent lactate dehydrogenase (LDHA) inhibitor GNE-140 on pancreatic cancer cells revealed that resistance to GNE-140 is attributable to an AMPK–mTOR–S6K-mediated switch in utilization from glycolysis to oxidative phosphorylation.

Analysis of the hydrolysis kinetics of strigolactone receptors using enzyme-activated fluorescent probes revealed that the catalytic triad histidine of the receptor forms a covalent interaction with the strigolactone hydrolysis product, the D ring.

A photoswitchable diacylglycerol enables spatiotemporal control of membrane translocation of C1-domain-containing proteins and protein kinase C activation to modulate calcium oscillations and vesicle release for synaptic transmission.

Histone deacetylase 6 (HDAC6) is a cytoplasmic HDAC that is unusual in having two adjacent catalytic domains. Kinetic data and X-ray crystallographic analyses of human and zebrafish HDAC6 enzymes provide insight into HDAC6 catalysis and its inhibition by small molecules.

X-ray crystallographic analysis reveals features of the tandem catalytic domains of histone deacetylase 6 (HDAC6), their inhibition by small molecules and functional insights into the enzyme's role in tubulin deacetylation.

Glucose metabolism has long been thought to operate with exquisite specificity and near-optimal efficiency. New findings show, however, that two glycolytic enzymes produce minor products that inhibit other enzymes involved in central carbon metabolism unless they are further metabolized by a novel enzyme.

Hsp90 is an energy-consuming molecular chaperone that activates oncogenic proteins in a complicated multi-step reaction. Photoinduced electron transfer (PET) quenching experiments with a fluorescent reporter have now identified molecular transitions at multiple timescales in the chaperone cycle of Hsp90.

A small-molecule screen examining the inhibition of Arabidopsis hypocotyl growth and seed germination identified an antagonist of strigolactone signaling, soporidine, that interacted with the strigolactone receptor AtHTL and blocked Striga germination.

Structural and biochemical studies of the Notch O-glucosyltransferase Rumi in complex with its substrates inform on the catalytic mechanism for Rumi substrate recognition, and characterization of cancer mutations in Rumi reveals loss of enzyme activity.

Rational design of the RNA recognition motif (RRM) of Rbfox promotes sequence-specific interaction with the terminal loop of miR-21 precursor. Replacement of the Dicer PAZ domain with this engineered Rbfox RRM enables specific degradation of pre-miR-21.