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Terminal triple bonds feature in natural products, but their biosynthesis is little known. Now a terminal acetylenase has been characterized for substrate specificity for the first time, and an application to 'bio-click' chemistry has been shown by incorporation of the moiety into natural product scaffolds.
Validation of the cellular targets of microRNAs remains an ongoing priority. miR-CLIP, a new method based on psoralen crosslinking, immunoprecipitation and biotin affinity pulldowns, was applied to determine the miR-106a targetome, which included the H19 lncRNA.
Genetic evidence suggested jamABC from the jamaicamide biosynthetic pathway were responsible for the synthesis of the terminal alkyne functional group. Biochemical studies now confirm this activity and demonstrate the insertion of alkynes into two unrelated natural products.
Hydrogen peroxide regulates cell signaling pathways through oxidation of specific thiol proteins. A new study describes a relay system involving peroxiredoxin 2 as a peroxide sensor that oxidizes the mammalian transcription factor STAT3 via a mixed disulfide intermediate.
Understanding how tumor cells utilize metabolic pathways for proliferation may provide useful strategies for combating cancer. A Perspective discusses recent advances in cancer drug development that target specific aspects of mitochondrial biosynthesis and bioenergetics processes.
Disulfide trapping and FRET studies define an agonist-induced conformational change in mGlu2 from inactive symmetric dimers with an interface at transmembrane domains (TMs) 4 and 5 to an active state with TM6s serving as the dimer interface.
Biocatalysis can take advantage of an enzyme's inherent reactivity regardless of its physiological role, as shown for a terpene cyclase turned Brønsted acid catalyst after its active site pocket was mutated while the activated aspartic acid was retained.
Characterization of four enzymes involved in biosynthesis of the plant metabolite and anticancer agent noscapine completes this pathway and identifies an unusual acetyl protecting group strategy that defines the order of enzymatic steps.
A family of cyclic lipopeptide natural products named lysocins was isolated from a soil bacteria sample and was found to exhibit antimicrobial actions. Genetic and biochemical evidence showed that lysocin E targets bacterial menaquinone.
An NMR structure reveals that the C terminus of the ubiquitin-conjugating enzyme Ube2w is disordered, leading to specific pairings with disordered substrates; loss of this sequence causes decreased substrate binding and ubiquitin transfer activity.
Inhibitors of FKBP51 with antidepressive activity are selective over the related FKBP52 and bind FKBP51 by an induced-fit mechanism that causes a conformational change. The analogous conformational change in FKBP52 generates a strained conformation.
A redox relay was identified in mammalian cells where the H2O2-reactive protein peroxiredoxin-2 oxidizes the transcription factor STAT3, resulting in the formation of transcriptionally inactive disulfide-linked oligomers.
