Volume 15 Issue 8, August 2019

A new small molecule that targets the vacuolar H⁺-ATPase activates autophagy, inhibits mTORC1 signaling, and displays potential for clearing toxic protein aggregates involved in neurodegenerative diseases.

Using knowledge of their evolutionary origin, an automated platform has been developed to provide accurate de novo structural predictions of products from trans-acyltransferase polyketide synthases.

Hetz et al. discuss recent advances in the identification and optimization of small molecules targeting the unfolded protein response and the application of these small molecules in cancers, neurodegeneration and metabolic diseases.

A covalent ligand that targets C277 of ATP6V1A was identified resulting in enhanced v-ATPase activity, inhibition of mTORC1 signaling, increased lysosomal acidification, activation of autophagy and clearance of toxic protein aggregates.

The C termini sequences recognized by E3 ubiquitin ligase CHIP were identified via a peptide library screen. Caspase cleavage caused the exposure of aspartic acid at the C termini of Tau and caspase-6 that made them accessible to CHIP.

Characterization of multiple enzymes involves in biosynthesis of the aminocyclitol antibiotic pactamycin reveals a key step involving the glycosylation of an acyl carrier protein-bound intermediate by the promiscuous glycosyltransferase PtmJ.

Elucidation of a multi-enzyme pathway for degradation of the polysaccharide ulvan by Formosa agariphila provides tools to use ulvan biomass from marine algal blooms as feedstock for renewable sources of carbohydrates.

The TransATor application bioinformatically predicts chemical structures for the products of trans-acyltransferase polyketide synthases, enabling the characterization of new polyketide natural products from (unusual) bacterial sources.

A chemical probe BI-9321 for the PWWP1 domain of NSD3 and its inactive analog were identified. BI-9321 binds to the methyl-lysine binding site, reduces the association of NSD3 with chromatin and inhibits proliferation of acute myeloid leukemia cells.

Use of DNA-origami nanostructures to study lipid transfer between closely apposed membrane bilayers supports a model where phospholipids are transferred by extended synaptotagmin 1 between the endoplasmic reticulum and plasma membrane through a shuttle mechanism.

Male C. elegans excrete an N-acylated glutamine that acts via evolutionarily conserved nuclear hormone receptor and chemosensory pathways to counteract dauer diapause and accelerate sexual maturation of hermaphrodites, at the cost of shortening hermaphrodite lifespan.