Volume 9 Issue 5, May 2013

Pseudomonas aeruginosa uses several intertwined cell-cell communication systems, called quorum sensing (QS) systems, to control gene expression. A QS signal–dependent transcription factor called LasR is at the top of the network. Mutations in lasR inactivate QS, but a new study has revealed an alternate signaling pathway that allows Pseudomonas aeruginosa to bypass LasR and activate a subset of quorum-controlled genes in times of stress.

Metabolic aberrations affecting protein and DNA methylation are a potential source of cancer. A new study shows that the metabolic enzyme nicotinamide N-methyl-transferase, which is overexpressed in several types of tumors, can enhance cancer aggressiveness by draining methyl groups from S-adenosyl-methionine.

A study of an insect prenyltransferase demonstrates that the product specificity of this bifunctional enzyme can be regulated by the presence of different divalent metal cofactors, resulting, for example, in the production of the precursors for either insect defense compounds or developmental hormones.

Analysis of proteins within their native environment can confirm and extend in vitro–derived conclusions. NMR analysis of superoxide dismutase 1 in live human cells now corroborates previously identified steps on the maturation pathway and demonstrates copper-independent function of the chaperone CCS.

NNMT converts SAM to the stable metabolite 1-methylnicotinamide, which reduces the methylation potential of cancer cells and thereby alters their epigenetic state to heighten the expression of protumorigenic genes.

ATP-competitive inhibitors compete with the Hsp90 cochaperone Cdc37 for the ATP site in kinases, depriving kinases of access to protein quality control machinery and promoting their degradation. Thus, in addition to inhibiting the catalytic activity of kinases, ATP-competitive inhibitors can reduce the number of active kinases in a cell by promoting their degradation.

Proteins that sample multiple conformations in the absence of a ligand have been presumed to operate via a conformational selection mechanism. Single molecule FRET studies of maltose binding protein now cast doubts on that assumption.

Class IIa histone deacetylases (HDACs) are generally viewed as noncatalytic readers of acetylated lysines within proteins. Specific inhibitors of class IIa HDACs, based on a new zinc-binding scaffold, offer chemical probes to explore the biological function and potential druggability of this enzyme subclass.

Constrained ligands activate a canonical ER pathway via a common structural mechanism, whereas dynamic ligands rewire the canonical pathway; DBD-dependent activity interferes with canonical ER proliferative signals and associates with a strong anti-inflammatory effect.

Methylthiolation by radical SAM enzymes is thought to include the sacrificial breakdown of a second Fe-S cluster to generate the sulfur cosubstrate. A biochemical, spectroscopic and structural study of two methylthiotransferases shows these enzymes retain their clusters, using exogenous thiols to modify their targets.

IQS is a Pseudomonas aeruginosa quorum sensing molecule that functions during phosphate limitation and lies near the top of the QS signaling hierarchy.