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Ribosomal decoding is dependent on wobble base pairing, which frequently involves modified nucleotides in the tRNA anticodon loop. The discovery of a new guanidine-modified base, 2-agmatinylcytidine, in the tRNAIle of archaea uncovers the mechanism for AUA decoding in these organisms.
In contrast to perceived nonselectivity, biochemical profiling reveals that currently available HDAC inhibitors predominantly inhibit only class I and IIb HDAC enzymes. A new pan-selective inhibitor, obtained by screening a focused library, provides an important tool for studying class IIa HDACs.
Cycloheximide is a natural product that cell biologists have used for decades as a tool to arrest protein synthesis in eukaryotes. Biochemical data now refine our mechanistic view of how cycloheximide and structurally related analogs inhibit translational elongation.
Group II introns can act as mobile genomic elements and integrate into genomic DNA through reverse splicing. A selective nucleotide modification approach was used to show that the 2′-hydroxyl at the ribozyme 3′ terminus plays a catalytic role as a proton shuttle during reverse splicing.
Pd-catalyzed domino reactions have been shown to stitch together chemical groups to form more complex scaffolds. Now these methods are used in a diversity-oriented synthesis approach to make intricate natural product–like structures using simple sugars as starting materials.
Reversible cobalt complexation of alkynes is a critical step in some chemical transformations. New research shows this reaction can be used to specifically retrieve modified lipids from complex cellular mixtures, simplifying tracking and providing insights into lipid metabolism.
Differentiation of mouse myoblasts is coordinated with glycolysis, calcium/calcineurin signaling, chromatin acetylation and cholesterol biosynthesis. This is consistent with profiling of the intracellular metabolites that accompany myogenic differentiation and points to new targets for cancer differentiation therapy of rhabdomyosarcoma.
The prion strain phenomenon states that distinct amyloid conformations with different phenotypes and heritable states can arise from a single polypeptide. The decision about amyloid conformation is made at the level of the initial nucleus, where different nuclei will lead to different conformations.
Despite the need for new psychoactive drugs, there are few robust approaches for discovering novel neuroactive molecules. Development of a behavior-based high-throughput screen in zebrafish led to the discovery of molecules with neurological effects. Translating the complex behavioral phenotypes elicited by compounds into a simple barcode enabled identification of their mechanism of action.
Although tetracycline selects for tetracycline-resistant bacterial strains, degradation products of tetracycline are now shown to select for tetracycline-sensitive strains, providing a potential mechanism for the observed coexistence of antibiotic-sensitive and antibiotic-resistant bacteria in the environment.
Upregulation of PI(3)K signaling pathways is implicated in many diseases, and a number of inhibitors are currently in clinical development. The structure of a PI(3)Kδ kinase domain, along with co-complexes with a diverse range of inhibitors, reveals new insights into mechanisms of inhibition and suggests isoform-selective design strategies.
Differences in packing and solvent exposure of hydrophobic residues determine the interactions with cell membranes and toxicity of different oligomers of the model protein HypF-N.
