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The 20° tilt angle of β-strands within the transmembrane β-barrel formed by bacterial perfingolysin O reveals how helices in adjacent monomers select the proper hydrogen-bonding partner during assembly.
The use of PALM imaging to quantify enzyme localization on technically challenging heterogeneous substrates yields a new directionally dependent metric for describing substrate specificity, the application of which explains synergy between carbohydrate-binding domains from diverse cellulases.
IQS is a Pseudomonas aeruginosa quorum sensing molecule that functions during phosphate limitation and lies near the top of the QS signaling hierarchy.
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.
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.
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.
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.
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.
A new small-molecule inhibitor that selectively binds an internal cavity in HIF-2α allosterically disrupts HIF-2α–ARNT interaction in vitro and in cells. This compound should allow scientists to interrogate HIF-2α's activity in hypoxia and cancer cells.
One pathway for lysine biosynthesis uses a carrier protein, LysW, to protect the substrate. LysW is now shown to mediate entry of a second substrate into the same metabolic pathway, with structural and biochemical evidence identifying an amino acid motif that determines substrate specificity.
Hedgehog acyltransferase (Hhat) attaches a palmitate to Sonic hedgehog, but the importance of this enzyme has been difficult to discern. RU-SKI 43 is a potent and selective inhibitor of Hhat in vitro and in cells that will allow scientists to investigate the importance of Hhat for Shh signaling.
A conjugate generated by expressed protein ligation between an antibody targeting dendritic cells (DCs) and an immune-stimulating double-stranded DNA reveals that DCs can mediate both innate and adaptive immunity and represents its potential utility as a vaccine adjuvant.
NMR structures of the homodimeric repressor protein CylR2 collected from 25 °C to –16 °C provide glimpses of the molecular changes that occur during cold denaturation, yielding insights into protein folding and oligomerization.
Optovin is a small molecule that renders zebrafish embryos responsive to light through generation of singlet oxygen and activation of the TrpA1b channel, providing a new tool for optogenetics.
The VAS1 aminotransferase regulates the shade avoidance response in Arabidopsis thaliana by shunting metabolic flux away from auxin and ethylene, two growth regulatory plant hormones.
Bacteria find creative solutions to occupy a variety of environmental niches. A peptide isolated from a gold-associated microbe provides a new example of this adaptation, binding gold and precipitating it to protect the organism from metal toxicity.
Structural analyses reveal that CopA and CupA share a binuclear Cu(I) ion binding motif and that copper is trafficked from a low-affinity site on CupA to a high-affinity site in CopA, making CupA the first membrane-bound copper chaperone important in copper resistance.
A new protein engineering approach inserts metal-coordination motifs to stabilize natural protein interfaces while other favorable contacts are removed, yielding metal-inducible protein-protein interactions that have allowed the study of a self-assembling protein cage and the chemical labeling of its interior.