Small-molecule-based regulation of RNA-delivered circuits in mammalian cells

October 16th, 2018 by Tyler E. Wagner

Small-molecule-based regulation of RNA-delivered circuits in mammalian cells

Small-molecule-based regulation of RNA-delivered circuits in mammalian cells, Published online: 16 October 2018; doi:10.1038/s41589-018-0146-9

Engineering of small-molecule-responsive RNA-binding proteins enables chemical regulation of modified mRNA or RNA replicon expression within mammalian cells for applications in synthetic circuit design and RNA-centered therapeutics.
  • Posted in Nat Chem Biol, Publications
  • Comments Off on Small-molecule-based regulation of RNA-delivered circuits in mammalian cells

Trading on thionoesters

October 16th, 2018 by Caitlin Deane

Trading on thionoesters

Trading on thionoesters, Published online: 16 October 2018; doi:10.1038/s41589-018-0158-5

Trading on thionoesters

Structural insights into binding specificity, efficacy and bias of a β<sub>2</sub>AR partial agonist

October 16th, 2018 by Matthieu Masureel

Structural insights into binding specificity, efficacy and bias of a β2AR partial agonist

Structural insights into binding specificity, efficacy and bias of a β<sub>2</sub>AR partial agonist, Published online: 16 October 2018; doi:10.1038/s41589-018-0145-x

The active-state structure of a GPCR occupied by a partial agonist, β2AR with salmeterol, together with mutagenesis and biophysical studies, explains this ligand's unusual pharmacological profile.
  • Posted in Nat Chem Biol, Publications
  • Comments Off on Structural insights into binding specificity, efficacy and bias of a β<sub>2</sub>AR partial agonist

A new spot for PKR

October 16th, 2018 by Yiyun Song

A new spot for PKR

A new spot for PKR, Published online: 16 October 2018; doi:10.1038/s41589-018-0159-4

A new spot for PKR

Metabolic repair through emergence of new pathways in <i>Escherichia coli</i>

October 16th, 2018 by Sammy Pontrelli

Metabolic repair through emergence of new pathways in Escherichia coli

Metabolic repair through emergence of new pathways in <i>Escherichia coli</i>, Published online: 16 October 2018; doi:10.1038/s41589-018-0149-6

In response to the deletion of key genes involved in biosynthesis of the essential CoA precursor β-alanine, Escherichia coli overcomes this pathway damage by successively evolving alternative metabolic pathways.
  • Posted in Nat Chem Biol, Publications
  • Comments Off on Metabolic repair through emergence of new pathways in <i>Escherichia coli</i>

Chaperoning partners

October 16th, 2018 by Grant Miura

Chaperoning partners

Chaperoning partners, Published online: 16 October 2018; doi:10.1038/s41589-018-0157-6

Chaperoning partners

Small molecules that target group II introns are potent antifungal agents

October 15th, 2018 by Olga Fedorova

Small molecules that target group II introns are potent antifungal agents

Small molecules that target group II introns are potent antifungal agents, Published online: 15 October 2018; doi:10.1038/s41589-018-0142-0

High-throughput screening followed by an examination of structure–activity relationship-based optimization resulted in the identification of potent small-molecule inhibitors of group IIB intron splicing in fungal organisms.
  • Posted in Nat Chem Biol, Publications
  • Comments Off on Small molecules that target group II introns are potent antifungal agents

Compartmentalizing acid stress in bacteria

October 15th, 2018 by Colin Kleanthous

Compartmentalizing acid stress in bacteria

Compartmentalizing acid stress in bacteria, Published online: 15 October 2018; doi:10.1038/s41589-018-0148-7

A Donnan equilibrium causes an influx of chloride ions into the Escherichia coli periplasm when the bacterium finds itself in gastric fluid. The combination of low pH and high anion concentration drives proteins to aggregate, a potentially lethal event unless prevented by specific chaperones.

In vivo chloride concentrations surge to proteotoxic levels during acid stress

October 15th, 2018 by Frederick Stull

In vivo chloride concentrations surge to proteotoxic levels during acid stress

In vivo chloride concentrations surge to proteotoxic levels during acid stress, Published online: 15 October 2018; doi:10.1038/s41589-018-0143-z

Protonation of periplasmic protein carboxylic groups creates a Donnan equilibrium in the bacterial periplasmic space at low pH, leading to accumulation of Cl− and unfolding and aggregation of periplasmic proteins, which can be rescued by chaperones.
  • Posted in Nat Chem Biol, Publications
  • Comments Off on In vivo chloride concentrations surge to proteotoxic levels during acid stress

The splice is right

October 15th, 2018 by James Palacino

The splice is right

The splice is right, Published online: 15 October 2018; doi:10.1038/s41589-018-0147-8

Current drug discovery efforts focus on proteins because of their ability to form stable, structured pockets. A recent study demonstrates that targeting stable, structured bioactive RNA motifs, such as autocatalytic introns, may provide a novel method of expanding druggability and selectivity.