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In vitro evolution of synthetic polymers has been limited by a lack of methods for translating genetic information into synthetic libraries and for amplifying selected molecules. An in vitro selection system for peptide nucleic acids (PNA) now brings the evolution of functional PNA polymers within reach.
Gut bacteria utilize dietary and host oligosaccharides for nutrients. Structural and biochemical evidence now demonstrates a conserved catalytic mechanism but diverse substrate preferences for a family of glycoside hydrolases, explaining how they break down complex glycans.
Na+and substrate symport through Tyt1, a prokaryotic neurotransmitter:sodium symporter, requires an inversely oriented H+ gradient, maintaining an ionic counterbalance during neurotransmitter translocation that is facilitated by negatively charged amino acid residues.
The tetronate ring appears in several natural products, but the biosynthetic path to this structure has proven elusive. Reconstitution of a polyketide assembly line and in vitro assays with a chemically synthesized intermediate now point to a single enzyme as catalyzing ring formation.
Compounds targeting the ERK/MAPK pathway in C. elegans could influence germ cell fate, inducing oocyte differentiation of stem cells in worms that only make sperm. The oocytes generated were functional, as they were able to generate embryos and produce viable offspring.
Although rare, small molecules that covalently bind one non-enzyme protein could have important applications—for instance, as imaging and therapeutic agents. A newly designed ligand that selectively binds to transthyretin and reacts chemoselectively with a lysine provides enhanced efficacy over a noncovalent analog in inhibiting amyloid fibril formation.
The ribosomal protein L7Ae and its RNA partner were used to construct a synthetic translational regulator that can be used to activate or repress protein expression, even performing both functions at once. Repression in human cells is highly effective, rivaling the potency of RNAi.
Comparing the Michaelis constants and rates of inhibition of wild-type and mutant hydrogenases reveals the quantitative impact of amino acid changes on the diffusion rates of H2, CO and O2 and suggests design strategies for creating oxygen-tolerant hydrogenases.
The trafficking defect associated with the cystic fibrosis disease-linked allele of the CFTR chloride channel is alleviated by inhibitors of histone deacetylases, suggesting that altering the transcription of genes associated with protein misfolding can ameliorate disease.
The RNA-activated protein kinase PKR inhibits translation initiation by sensing long viral double-stranded RNA. A new report indicates that PKR is also activated by a cellular mRNA, but only when ribosomes are not initiating translation.
Two iron regulatory proteins (IRP1 and IRP2) regulate translation and/or stability of mRNAs encoding proteins required for iron storage, acquisition and utilization. Rather than IRP2 directly sensing iron concentrations, iron has been shown to regulate the level of the SKP1-CUL1-FBXL5 E3 ubiquitin ligase protein complex, which is responsible for IRP2 degradation.
Vibrio cholerae produces cholera autoinducer-1 (CAI-1), a signaling molecule previously believed to be synthesized by the CqsA enzyme. Here it is shown that CqsA does not directly synthesize CAI-1; instead, it synthesizes amino-CAI-1, which is then converted into CAI-1 in a CqsA-independent manner.
A unique heterotrimeric assembly of individually inactive paralogs, two of which are also involved in regulating phosphatase activity, creates one of the key enzymes of coenzyme A biosynthesis in yeast, pointing to the possibility of a previously undescribed cross-talk between metabolic and signaling pathways.