Volume 6 Issue 9, September 2010

Many nuclear and cytoplasmic proteins are post-translationally modified by both O-GlcNAc and phosphate, but determining whether a single copy of a protein bears multiple modifications remains a challenge. A new analytic approach reveals a surprising correlation between phosphorylation and the O-GlcNAc modification.

Many natural products are decorated with oxygenated nitrogens, but enzymes capable of forming a stable nitroso species have been elusive. A new study reports the identification of a copper-containing C-nitrososynthase that tightly controls the oxidation state of an aromatic amine to yield the natural product 4-hydroxy-3-nitrosobenzamide.

Subterranean termite colonies are founded by a single king and queen. However, the king generally outlives the queen, and an optimal number of secondary termite queens must be produced to meet the reproductive needs of the colony. A recent study explains the chemical basis of this biological process.

Manipulation of stem cells is an important therapeutic goal that has proven difficult to achieve. A recent report describes a novel in vivo small-molecule screen and identifies a modulator of mammalian neurogenesis that partially reverses age-related declines in cognition.

A variety of natural C-nitroso compounds are known, but the path to these important functional groups has been a mystery. Elucidation of the biosynthetic route to an iron chelator now reveals a tyrosinase-like copper-containing monooxygenase as responsible for the transformation.

Current methods to investigate glycosylation allow the identification of modification sites but provide limited additional information. A new strategy using polymers to label specific sugars now shows a huge variety in the occupancy of known glycosylation sites as well as unexpected interplay between post-translational modifications.

Instability of (CTG)•(CAG) repeats in microsatellite DNA has been linked to numerous neurological diseases. Probing trinucleotide repeat structures using engineered zinc-finger nucleases provides evidence that DNA hairpins form in vivo and are linked to replication-dependent genomic instability.

Although FPPS is a potential anti-cancer target, the high bone affinity of nitrogen-containing bisphosphonates, FPPS inhibitors used clinically to treat bone disease, has prevented their development as cancer therapeutics. Using fragment-based drug discovery, non-bisphosphonate inhibitors were discovered that bind in a previously undescribed allosteric pocket.

A chemical array screen identifies a small-molecule inhibitor of pirin that inhibits its interaction with the oncoprotein Bcl3 and decreases the expression of the tumor mobility protein SNAI2. As a result, the compound perturbs the migration of melanoma cells that have high pirin expression levels.

Probing the biological location and function of transition metals has proven difficult. X-ray fluorescence microscopy in combination with an array of metal chelators now provides a way to interrogate zinc in maturing mouse oocytes, demonstrating a role for this metal in cell division.

Biotin synthesis is known to include a pimelate intermediate, the construction of which is controversial. Genetic manipulations and chemical feeding now demonstrate that the two mystery enzymes in the process create and cleave a methyl ester that sends a biotin precursor into the fatty acid synthesis machinery.