Brief Communications in 2016

The synergistic effect of the GPCR β₂AR on signaling through another GPCR, PTHR, is explained by the release of Gβγ from the heterotrimeric Gα_iβγ protein, activating adenylate cyclase AC2 and subsequent prolonged cAMP signaling in internal compartments

The development of small-molecule fluorescent probes through addition of a lipidated cysteine residue next to a caged fluorophore enables detection of endogenous cysteine depalmitoylation by acyl–protein thioesterases in vitro and in live cells.

The iron protein components of bacterial nitrogenases are capable of reducing carbon dioxide (CO₂) to carbon monoxide (CO) in the absence of their catalytic partners, mimicking the activity of CO dehydrogenase.

A strategy called footprinting of long 7-deazaguanine-substituted RNA (FOLDeR) enables the identification of RNA G quadruplexes in long RNA.

Small-molecule control of transcriptional activation and genome editing was achieved by tethering inducible protein degron domains to an engineered CRISPR–Cas9 system.

A genetic screening approach using chemically mutagenized haploid mouse embryonic stem cells combined with next-generation sequencing identified recessive suppressor point mutations that elicit resistance to 6-thioguanine.

Mass spectrometry analysis of stromal extracts reveal a peptidolytic cascade in the plant chloroplast consisting of oligopeptidases and aminopeptidases that mediates the complete degradation of signal peptides to free amino acids.

Unlike their bacterial counterparts, fungal nonribosomal peptide synthetases utilize a terminal condensation-like (C_T) domain to form macrocycles, details of which are illuminated by structures of a C_T domain and neighboring thiolation domain.

The synthetic bioinformatic natural products (syn-BNPs) approach identifies putative natural products that are validated directly by independent synthesis. Its application led to the identification of humimycins, non-ribosomal peptides that have antimicrobial activity in mice.

ADP-ribosylation is a post-translational protein modification that regulates numerous cellular pathways. An approach involving histone purification, partial filter-aided digestion and ETD mass spectrometry reveals that serine residues in histone proteins are ADP-ribosylated.

A proteomic approach in Saccharomyces cerevisiae identifies cytochrome b reductase (Cbr1) as an NADH-dependent electron donor for diphthamide biosynthesis 3 (Dph3), a protein that serves as an electron source for diphthamide biosynthesis and tRNA modification.

A chemoproteomics approach utilizing the thermal shift assay and quantitative MS resulted in the identification of phenylalanine hydroxylase as an off-target of the histone deacetylase inhibitor panobinostat.

Nikkomycins and polyoxins are peptidylnucleosides with antifungal activity. The biosynthetic routes to these natural products share a bicyclic intermediate formed by a carbon radical–centered ring closure catalyzed by the radical SAM enzymes NikJ or PolH.

A high-throughput screen against the E. coli tetracycline-resistance efflux pump TetA identifies two ‘selection-inverting’ compounds that swap tetracycline resistance for resistance to another antibiotic, paving the way for two-phase antibiotic treatment protocols.

The glycosyltransferase OGT cleaves a substrate, HCF-1, via a glutamyl-sugar intermediate, defining a reaction mechanism that requires UDP-GlcNAc and involves the formation of an internal pyroglutamate that undergoes spontaneous backbone hydrolysis.

A selective inhibitor of the With-No-Lysine (K) (WNK) kinase family reduces blood pressure and increases electrolyte excretion in hypertensive rats.

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.

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.

Nemamides are hybrid polyketide–nonribosomal peptide natural products that were identified by metabolomics profiling in Caenorhabditis elegans and are involved in the organism's survival response to nutrient-deficient conditions.

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.