Articles in 2016

High-throughput screening identified a small-molecule compound that targets the active conformation of HER2 and is effective against growth-factor-mediated drug resistance.

An AFM-based single-molecule approach shows how the chaperone and insertase YidC stabilizes E. coli LacY in the unfolded state and assists LacY to insert and fold transmembrane structural segments in random order until folding of the native state is complete.

Adeno-associated viral delivery of an orthogonal tRNA synthetase-tRNA system enables the encoded incorporation of non-natural amino acids into proteins in neuronal cells, in brain slices and in living mice.

A small molecule inhibits CDK12 and CDK13 activity through covalent modification of Cys residues and reveals a role of the two kinases in regulating Pol II processivity and super-enhancer-driven transcription factor and DNA damage response gene expression.

Biochemical and genetic strategies demonstrate that the antifungal natural product beauvericin targets both multidrug efflux and TOR signaling to limit drug resistance and to sensitize resistant pathogens to drug treatment during infection.

Probes based on the photoactive yellow protein tag for monitoring the consequences of glycosylation on GLUT4 traffic reveal that glycosylation is important for plasma membrane retention of the glucose transporter.

A high-throughput screen using a mass-spectrometry-based assay results in the identification of LRE1 as an inhibitor of HCO₃⁻/Ca²⁺-regulated soluble adenylyl cyclase activity. LRE1 interacts with the HCO₃⁻ binding site (BBS) to block cAMP formation.

Detailed biophysical, microscopy, and statistical analyses of hydrocarbon-stapled peptide variants revealed how a combination of critical parameters such as hydrophobicity, α-helicity and isoelectric point influence cellular permeability.

Variations in pathway off-loading and module skipping within a hybrid polyketide synthase–nonribosomal peptide synthetase lead to the production of a collection of precursors to colibactin, a genotoxic compound produced by gut bacteria.

A combination of statistical analysis, quantum mechanics calculations and biophysical analytical approaches shows that methionine oxidation increases its interactions with aromatic side chains, interactions that are important for intraprotein and interprotein interactions.

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 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.

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.

The LARGE glycosyltransferase generates a repeating disaccharide on α-dystroglycan, an extracellular matrix receptor essential for muscle function. A structural study defines a unique binding mode between the LARGE-generated oligosaccharide and the matrix protein laminin.

A biosensor based on the GABA_A receptor with a readout consisting of quenching and recovery of biomolecular fluorescence in live cells is used in a screen to identify new interacting ligands for the receptor benzodiazepine site.