Research articles

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.

Microarray analysis of butein-treated adipocytes results in the identification of the PR domain containing 4 (Prdm4) transcription factor, which stimulates WAT browning and lipolysis and protects against diet-induced obesity.

Crotonylated lysine residues within histones are linked to transcriptional activation in a process involving histone mark ‘reader’ proteins. Crystallographic analysis of the YEATS domain of the Taf14 protein reveals a mode of crotonylated histone mark recognition via a π-sandwich motif.

The attachment of a nuclear export sequence to the blue light-sensitive LOV2 domain mediates rapid and reversible protein export of the ubiquitin ligase Bre1 with light exposure, resulting in changes in histone ubiquitylation and methylation.

A synthetic biochemistry approach optimizes a glucose breakdown pathway to produce acetyl-CoA as a building block for polyhydroxybutyrate bioplastic production in the test tube.

YihQ hydrolyzes the glycosidic linkage in sulfoquinovosyl diacylglyceride (SQDG) to form sulfoquinovose (SQ). Crystal structure analysis reveals active site residues required for the specificity of YihQ for SQ and allows the identification of other YihQ homologs.

Expansion of the genetic code to noncanonical amino acids (NCAAs) has been limited by the lack of evolutionary pressure for organismal dependence on the NCAA. Linking bacterial survival to an engineered β-lactamase that requires a non-natural tyrosine analog engenders diverse bacteria with a stable, expanded genetic code.

Post-translational modifications (PTMs) of lysine side chains are important mediators of protein-protein interactions, particularly in chromatin. Photo-lysine, a diazirine analog of lysine, provides a tool to covalently capture proteins that bind lysine and its PTMs.

Cremeomycin is a diazo-containing natural product. Assignment of the functions of individual enzymes in the gene cluster for cremeomycin biosynthesis reveals a pathway by which Streptomyces cremeus converts L-aspartic acid into the nitrous acid needed for diazotization chemistry.

The biosynthesis of iridoids, a class of bicyclic monoterpenes, features an atypical cyclization reaction catalyzed by iridoid synthase (ISY). Crystallographic and biochemical characterization of ISY from Catharanthus roseus provides insights into the ISY enzymatic mechanism and highlights similarities with the homologous progesterone 5β-reductase.

Structure and functional characterization of BpHep, a heparanase from the invasive pathogenic bacterium Burkholderia pseudomallei, defines its glycosaminoglycan recognition mechanism and its catalytic mechanism as an endo-acting glycoside hydrolase.

Some polyketide synthase pathways include branching modules that insert branched monomers into polyketide products. In vitro reconstitution using swapped domains now shows that the mysterious branching (B) domain and the homologous X domain in these modules have structural rather than catalytic roles.

The combination of a light-activated receptor tyrosine kinase and a fluorescent MAPK/ERK reporter results in the development of an optogenetics-based cell screening method to identify small-molecule inhibitors of RTK signaling.

The identification and characterization of two cytochromes P450 from cabbage establish the biochemical basis for synthesizing brassinin-based phytoalexins, using two different routes of S-heterocyclization to construct these important vegetable compounds.

High-throughput chemical screening identified several groups of compounds that selectively block superoxide production from the outer Q-binding site of mitochondrial complex III and protect against ROS-induced oxidative stress in pancreatic β cells.