Volume 10 Issue 7, July 2014

Carbonates are known to exist in natural products, but their biosynthesis has not been linked to any enzymes. An unusual fungal Baeyer-Villiger monooxygenase CcsB is now revealed to catalyze an in-line carbonate formation via a two-step mechanism of oxygen atom insertions.

Recent studies have identified the existence of modified cytosine bases in DNA that result from ten eleven translocation (Tet)-mediated oxidation of 5-methylcytosine. The demonstration that Tet oxidizes thymine to 5-hydroxymethyluracil has implications for our current view of DNA metabolism.

A study in this issue reports the 5-HT₆ receptor as a new cyclin-dependent kinase 5 (Cdk5) substrate and reveals its noncanonical pathway, which mediates neuronal differentiation in hippocampus and striatum by interacting with Cdk5 and Cdc42 in an agonist-independent manner.

Therapeutic drug monitoring is vital for maintaining drug concentrations within the body in real time, maximizing therapeutic effects while minimizing the risk of harmful overdosing or wasteful underdosing. Semisynthetic fusion proteins now provide a straightforward strategy for drug monitoring by simply taking a picture of glowing paper.

Carbonates exist in a few natural products, but their biosynthetic origins have been unclear. Genetic and biochemical characterization of a flavin-dependent monooxygenase from the cytochalasin cluster now demonstrates conversion of a ketone into a carbonate prior to other tailoring steps.

Genetic code reprogramming has generally focused on changing the translation step of protein expression, altering what each codon specifies. Mutations in the peptidyl transferase center, along with compensatory mutations in the C-termini of tRNAs, now provide an alternate method to create fully orthogonal ribosomes.

The allosteric binding of MSI-1436 to the intrinsically disordered C-terminal region of PTP1B promotes a conformational change to generate a compact inactive structure, validating the use of MSI-1436 to inhibit HER2-mediated tumorigenesis.

Structure-guided peptide phage display combined with activity-based sorting results in the identification of zymogen activator peptides (ZAPtides) that selectively bind and activate the serine protease–like pro-HGF zymogen to promote Met signaling.

5-hydroxymethyluracil (hmU) is an oxidative DNA lesion and a potential intermediate in DNA repair–coupled DNA demethylation pathways. Isotopic labeling and MS reveal that hmU is produced directly by Tet-mediated oxidation of thymine in mouse embryonic stem cells, suggesting a functional role for hmU in stem cells.

PIP₂ binds via electrostatic interactions to the N terminus of the dopamine transporter (DAT) to modulate its function in dopamine efflux. This regulation is necessary for Drosophila locomotor activity induced by the DAT substrate amphetamine.

The serotonin receptor 5-HT₆ interacts with a network of proteins that includes Cdk5. Functionally, Cdk5 phosphorylates the receptor at S350 and modulates its activity in inducing neuronal differentiation in a model neuroblastoma cell line and neurite growth in primary neurons.

The combination of synthetic ligands, luminescent proteins and binding proteins converts a well-established ligand-sensing system into a tunable and quantitative reporter for drug concentrations in blood, as demonstrated with six different drugs and using a simple digital camera.

Light defines life on Earth through processes such as photosynthesis and vision, but also plays an increasingly important role in scientific research as a readout or regulator of biomolecular function. In this issue, we present a collection of articles that explore light in biology.