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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.
Successive rounds of selection of an RNA library in a mouse cancer model resulted in the identification of an aptamer that specifically bound a cancer-associated protein, providing an in vivo approach for identifying RNA motifs that can reveal and potentially inhibit tumor-specific targets.
Spatial- and time-resolution FRET methods on single pre-translocation ribosome complexes reveal that aminoglycoside antibiotics inhibit translocation by altering structural and dynamic parameters to stabilize the binding of aminoacyl tRNAs to the classical A-site of the ribosome.
Allantoin catabolism provides nitrogen, carbon and energy for several species, but the biochemical route to these resources in some species was unclear. A multidimensional bioinformatic search across organisms has now led to the identification of two enzymes that complete the degradation pathway.
Quorum sensing refers to a signaling mechanism allowing the behavior of bacterial populations to be coordinated based on cell density. Physical isolation of individual bacterial cells revealed that a single bacterium can respond to quorum sensing signals resulting in genetic reprogramming and enhanced.
Errors in functional annotations can cause significant problems in later research. A new method to identify misannotations by analyzing the genomic context correlations corrects these errors, such as in the reassignment of genes now demonstrated to have roles in leucine and fatty acid degradation.
Binding of HIV-1 Nef to host cell membranes is a biphasic process that involves electrostatic curvature-sensitive Nef-lipid interactions followed by a slower formation of an amphipathic helix. Nef action on the membrane may promote curvature and subsequent endocytosis of the host-cell proteins.