Volume 14 Issue 11, November 2018

The prodrug dimethyloxalylglycine (DMOG) is a well-known tool compound used to study hypoxia. New findings reveal that DMOG also inhibits glutamine metabolism and can be exploited to selectively kill some cancer cells, highlighting important caveats when using DMOG for hypoxia studies.

The proteome-wide application of a probe that selectively labels cysteine residues oxidized to the sulfinic acid form reveals the mammalian S-sulfinylome and uncovers novel substrates of the sulfinyl reductase sulfiredoxin, opening yet unexplored realms of cysteine-based redox regulation.

A Donnan equilibrium causes an influx of chloride ions into the Escherichia coli periplasm when the bacterium finds itself in gastric fluid. The combination of low pH and high anion concentration drives proteins to aggregate, a potentially lethal event unless prevented by specific chaperones.

An electrophilic diazene probe (DiaAlk) enables capture and proteomic analysis of cysteine S-sulfinylation modifications, thus illuminating dynamic responses to oxidative stress and enabling the identification of new substrates of sulfiredoxin.

In response to the deletion of key genes involved in biosynthesis of the essential CoA precursor β-alanine, Escherichia coli overcomes this pathway damage by successively evolving alternative metabolic pathways.

A comparative genomic approach identified a novel acetate-dependent tRNA-modifying enzyme that catalyzes RNA acetylation with a mechanism similar to tRNA aminoacylation. This modification maintains decoding fidelity in protein synthesis.

mmBCFAs are endogenous fatty acids synthesized from BCAAs by brown and white adipose tissue via CrAT and FASN promiscuity. BCAA catabolism and mmBCFA lipogenesis are decreased by obesity-induced adipose hypoxia and influenced by the microbiome.

High intracellular concentrations of the α-ketoglutarate analog N-oxalylglycine, owing to MCT2-mediated transport of its newly described prodrug MOG, inhibit multiple enzymes in glutamine metabolism and selectively kill MCT2-expressing cancer cells.

Engineering of small-molecule-responsive RNA-binding proteins enables chemical regulation of modified mRNA or RNA replicon expression within mammalian cells for applications in synthetic circuit design and RNA-centered therapeutics.

Protonation of periplasmic protein carboxylic groups creates a Donnan equilibrium in the bacterial periplasmic space at low pH, leading to accumulation of Cl⁻ and unfolding and aggregation of periplasmic proteins, which can be rescued by chaperones.

The active-state structure of a GPCR occupied by a partial agonist, β₂AR with salmeterol, together with mutagenesis and biophysical studies, explains this ligand's unusual pharmacological profile.