Volume 15 Issue 4, April 2019

A small molecule was identified that binds to a unique site on the pro-apoptotic protein BAX, stabilizing the protein structure allosterically and preventing the conformational activation to a pore former by BH3 proteins.

The N⁶-methyladenosine modification next to the 5′ RNA cap has dynamic regulatory functions. Recent findings show that this modification regulates the splicing and translational activity of different classes of RNAs.

Potassium channels allow the passage of potassium ions across membranes at rates approaching the diffusion limit while maintaining exquisite selectivity between ion species. Single-molecule studies now reveal that the selectivity filter of these proteins transitions between different conformations.

Powerful combinatorial peptide library methods allow the discovery of peptide leads from diverse libraries. A new platform based on tandem mass spectrometry peptide sequencing coupled with high-performance size-exclusion chromatography enables identification of high-affinity peptidic ligands from focused libraries.

Using biochemical and NMR studies, a class of small-molecule inhibitors termed BAX activation inhibitors were found to bind directly to a previously unrecognized pocket of inactive BAX and allosterically inhibit conformational changes in BAX.

Enzymes from two discrete biosynthetic gene clusters in the entomopathogenic bacterium Xenorhabdus szentirmaii cooperate to produce a diverse array of phenazine natural products, including phenazine–peptide and phenazine–polyketide derivatives.

Two different methylation states of the adenosine adjacent to the snRNA cap are found in the biogenesis process of snRNAs, Am and m6Am, whose levels are regulated by FTO and are related to alternative pre-mRNA splicing.

Combining X-ray structures, surface plasmon resonance and hydrogen-deuterium exchange–mass spectrometry, a class of highly selective inhibitors was found to bind to an active state of PI3Kγ breaking a conformational ‘lock’ important for activation of PI3Kγ.

A small molecule that inhibits the interaction between BRAG2, a guanine-nucleotide exchange factor for the small GTPase Arf, and the membrane affects exchange factor function at the Golgi and suggests a role for BRAG2 in breast cancer.

Structural analysis of HIF-2α in complex with agonists and antagonists reveal that chemical ligands regulate the activity of HIF-2α by affecting the stability of the HIF-2α–ARNT heterodimer via redirecting residues in the PAS-B pocket.

Single-molecule FRET shows that a loop, which forms the selectivity filter in the bacterial inwardly rectifying K⁺ channel KirBac1.1, transitions between constrained and dilated conformations depending on ion occupancy of the filter.

Neopinone isomerase catalyzes the isomerization of the opiate alkaloid neopinone to codeinone, driving the biosynthesis of codeine and morphine and preventing accumulation of their isomers neopine and neomorphine.

Chemoproteomic mapping of fumarate sensitive cysteines in a hereditary leiomyomatosis and renal cell carcinoma cell line revealed a critical cysteine in the protein–protein interaction interface of the SWI–SNF complex.

A genetically encoded array to amplify signals for live-cell single-molecule fluorescence imaging allows unlimited temporal resolution through exchange of fluorophores and can be used to monitor the dynamics of histones, kinesins and integrins.

Affinity-based selection in solution enables the identification of high-affinity ligands for disrupting the MDM2–p53 interaction and binding to the HIV capsid protein from libraries of both linear and cyclic peptides containing non-canonical amino acids.

A comprehensive analysis of the effect of the side chain composition of nucleic acid polymers revealed that the polarity of the side chains determines the performance of polymers during in vitro selections for protein binding.