Resilient living materials built by printing bacterial spores

December 2nd, 2019 by Lina M. González

Nature Chemical Biology, Published online: 02 December 2019; doi:10.1038/s41589-019-0412-5

3D printing agarose hydrogels embedded with Bacillus subtilis spores produce custom-shaped materials that are resistant to environmental stresses, while the bacteria maintain the ability to germinate on the surface and respond to stimuli.

Targeting the interaction of AIMP2-DX2 with HSP70 suppresses cancer development

December 2nd, 2019 by Semi Lim

Nature Chemical Biology, Published online: 02 December 2019; doi:10.1038/s41589-019-0415-2

The cellular stability of an oncogenic factor, AIMP2-DX2, is increased via association with HSP70. Interference with this interaction by a small-molecule compound promotes ubiquitin-mediated degradation of AIMP2-DX2 and reduces cancer cell growth.
  • Posted in Nat Chem Biol, Publications
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Guided nuclear exploration increases CTCF target search efficiency

December 2nd, 2019 by Anders S. Hansen

Nature Chemical Biology, Published online: 02 December 2019; doi:10.1038/s41589-019-0422-3

Single-particle tracking and mathematical modeling methods reveal the searching mechanism of CTCF for its cognate sites on DNA. An RNA-binding region in CTCF mediates its trapping in small zones and increases its target search efficiency.

Computational design of G Protein-Coupled Receptor allosteric signal transductions

December 2nd, 2019 by Kuang-Yui Michael Chen

Nature Chemical Biology, Published online: 02 December 2019; doi:10.1038/s41589-019-0407-2

A computational approach for designing GPCRs with new signaling functions including allosteric signaling properties yielded D2 receptor variants with predictable G-protein signaling responses, some with enhanced potency and responses to dopamine.
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The manifold roles of microbial ribosomal peptide-based natural products in physiology and ecology [Metabolism]

November 29th, 2019 by Yanyan Li, Sylvie REBUFFAT

The ribosomally synthesized and posttranslationally modified peptides (RiPPs), also called ribosomal peptide natural products (RPNPs), form a growing superfamily of natural products that are produced by many different organisms and particularly by bacteria. They are derived from precursor polypeptides whose modification by various dedicated enzymes helps establish a vast array of chemical motifs. RiPPs have attracted much interest as a source of potential therapeutic agents, and in particular as alternatives to conventional antibiotics in order to address the bacterial resistance crisis. However, their ecological roles in Nature are poorly understood and explored. The present review describes major RiPP actors in competition within microbial communities, the main ecological and physiological functions currently evidenced for RiPPs, and the microbial ecosystems that are the sites for these functions. We envision that the study of RiPPs may lead to discoveries of new biological functions and highlight that a better knowledge of how bacterial RiPPs mediate inter-/intra-species and inter-kingdom interactions will hold promise for devising alternative strategies in antibiotic development.

Multiple distinct pathways lead to hyperubiquitylated insoluble TDP-43 protein independent of its translocation into stress granules [Protein Synthesis and Degradation]

November 28th, 2019 by Friederike Hans, Hanna Glasebach, Philipp J. Kahle

Insoluble, hyperubiquitylated TAR DNA binding protein of 43 kDa (TDP-43) in the central nervous system characterizes frontotemporal dementia and ALS in many individuals with these neurodegenerative diseases. The causes for neuropathological TDP-43 aggregation are unknown, but it has been suggested that stress granule (SG) formation is important in this process. Indeed, in human embryonic kidney HEK293E cells, various SG forming conditions induced very strong TDP-43 ubiquitylation, insolubility and reduced splicing activity. Osmotic stress–induced SG formation and TDP-43 ubiquitylation occurred rapidly and coincided with colocalization of TDP-43 and SG markers. Washout experiments confirmed the rapid dissolution of SGs, accompanied by normalization of TDP-43 ubiquitylation and solubility. Surprisingly, interference with the SG process using a protein kinase R–like endoplasmic reticulum kinase inhibitor (GSK2606414) or the translation blocker emetine did not prevent TDP-43 ubiquitylation and insolubility. Thus, parallel pathways may lead to pathological TDP-43 modifications independent of SG formation. Using a panel of kinase inhibitors targeting signaling pathways of the osmotic shock inducer sorbitol, we could largely rule out the stress-activated and extracellular signal-regulated protein kinase modules and glycogen synthase kinase 3β. For arsenite but not for sorbitol, quenching oxidative stress with N-acetylcysteine did suppress both SG formation and TDP-43 ubiquitylation and insolubility. Thus, sodium arsenite appears to promote SG formation and TDP-43 modifications via oxidative stress, but sorbitol stimulates TDP-43 ubiquitylation and insolubility via novel pathway(s) independent of SG formation. In conclusion, pathological TDP-43 modifications can be mediated via multiple distinct pathways for which SGs are not essential.
  • Posted in Journal of Biological Chemistry, Publications
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[ASAP] Structural and Biochemical Investigations of the [4Fe-4S] Cluster-Containing Fumarate Hydratase from <italic toggle=”yes”>Leishmania major</italic>

November 27th, 2019 by

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.9b00923

A computational framework to explore large-scale biosynthetic diversity

November 25th, 2019 by Jorge C. Navarro-Muñoz

Nature Chemical Biology, Published online: 25 November 2019; doi:10.1038/s41589-019-0400-9

Two bioinformatic tools, BiG-SCAPE and CORASON, enable sequence similarity network and phylogenetic analysis of gene clusters and their families across hundreds of strains and in large datasets, leading to the discovery of new natural products.
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Discovery of an antivirulence compound that reverses <i>β</i>-lactam resistance in MRSA

November 25th, 2019 by Omar M. El-Halfawy

Nature Chemical Biology, Published online: 25 November 2019; doi:10.1038/s41589-019-0401-8

A potent inhibitor of the MRSA virulence regulator, GraR, reverses methicillin resistance, inhibits biofilm formation, limits bacterial survival in macrophages and attenuates virulence in vitro, synergizing with cationic antimicrobial peptides.
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Global targeting of functional tyrosines using sulfur-triazole exchange chemistry

November 25th, 2019 by Heung Sik Hahm

Nature Chemical Biology, Published online: 25 November 2019; doi:10.1038/s41589-019-0404-5

Sulfur-triazole exchange (SuTEx) chemistry is a tunable platform for covalent chemoproteomic probes that selectively target tyrosines, used to identify residues with enhanced nucleophilicity and monitor activation of phosphotyrosine sites.
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