Volume 12 Issue 9, September 2016

A high-throughput screen in the model plant Arabidopsis unveils leads for potential agents to combat Striga, a devastating root parasitic weed that affects food crops in Sub-Saharan Africa.

Chemical probes and drugs often bind to functional domains on disease-relevant proteins. A study suggests a chemical genetic approach to establish on-target effects by swapping the targeted domain, affording resistance to pharmacological inhibition while retaining functionality.

Crystal structures of both catalytic domains of HDAC6 provide insights into the mechanisms of deacetylation for their specific substrates and a structural basis for understanding selective inhibition of HDAC6.

A Perspective focused on post-translational modifications of histone proteins and their selective recognition by epigenetic 'readers' highlights the importance of structural insights in understanding these key interactions in gene expression regulation.

An activity-based proteomic strategy identifies PLA2G4E as the calcium-dependent N-acyltransferase that generates an unusual triacylated class of lipids, the NAPEs, which are precursors to bioactive lipids including the endogenous cannabinoid anandamide.

Acute myeloid leukemia (AML) cells require BRD9 to regulate MYC gene expression and prevent myeloid differentiation. Selective inhibition of BRD9 using a chemical probe that was validated using a resistant bromodomain-swap allele of BRD9 limits AML cell growth.

A reactivity-based probe containing an iron-sensitive 1,2,4-trixolane ring conjugated to a small molecule payload combined with a high-throughput immunofluorescence assay enables the selective detection of labile intracellular ferrous iron.

The use of activity-based chemical probes revealed that Scribble is palmitoylated at cysteine residues by the palmitoyl acyltransferase ZDHHC7. Loss of Scribble palmitoylation results in loss of cell polarity and its tumor suppressor activity.

Photoactivable caged morpholinos combined with whole-transcriptome sequencing revealed Tbx16-mediated suppression of posterior hox genes in zebrafish mesodermal progenitor cells.

Structural and biochemical analysis of the recently discovered env25 pistol ribozyme reveal an active site containing a pseudoknot that enforces in-line nucleophilic attack at the scissile phosphate and positions nucleotides for general acid and general base catalysis.

Evolution of RNA aptamers that act allosterically by recognizing and stabilizing specific conformations, including active, inactive, and ligand-specific conformations of the GPCR β₂-adrenergic receptor, bound to pharmacologically distinct ligands.

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.

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 bacterial NAD-decapping enzyme, NudC, in complex with NAD or its cleavage product NMN reveal the critical residues for substrate recognition and the preference of NudC for NAD-capped RNA.

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.

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.

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.