Discovery of a ZIP7 inhibitor from a Notch pathway screen

January 14th, 2019 by Erin Nolin

Discovery of a ZIP7 inhibitor from a Notch pathway screen

Discovery of a ZIP7 inhibitor from a Notch pathway screen, Published online: 14 January 2019; doi:10.1038/s41589-018-0200-7

A cell-based phenotypic screen identifying inhibitors of Notch signaling led to the discovery of NVS-ZP7-4, which blocks the activity of the zinc transporter SLC39a7 (ZIP7) and induces cell death through an ER stress mechanism.

IFITM3 directly engages and shuttles incoming virus particles to lysosomes

January 14th, 2019 by Jennifer S. Spence

IFITM3 directly engages and shuttles incoming virus particles to lysosomes

IFITM3 directly engages and shuttles incoming virus particles to lysosomes, Published online: 14 January 2019; doi:10.1038/s41589-018-0213-2

Live-cell imaging and virus trafficking studies show that the host innate immune receptor IFITM3 localizes with endocytic vesicles that fuse with incoming viruses to ultimately enhance their traffic to lysosomes.
  • Posted in Nat Chem Biol, Publications
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Selective and reversible modification of kinase cysteines with chlorofluoroacetamides

January 14th, 2019 by Naoya Shindo

Selective and reversible modification of kinase cysteines with chlorofluoroacetamides

Selective and reversible modification of kinase cysteines with chlorofluoroacetamides, Published online: 14 January 2019; doi:10.1038/s41589-018-0204-3

Discovery and exploitation of inherent reaction features of chlorofluoroacetamide (CFA) as a warhead such as low off-target activity and reversible reactivity with cysteine enable specific covalent inhibition of targeted kinases.
  • Posted in Nat Chem Biol, Publications
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Complete reconstitution of the diverse pathways of gentamicin B biosynthesis

January 14th, 2019 by Yeon Hee Ban

Complete reconstitution of the diverse pathways of gentamicin B biosynthesis

Complete reconstitution of the diverse pathways of gentamicin B biosynthesis, Published online: 14 January 2019; doi:10.1038/s41589-018-0203-4

The reconstitution of gentamicin B biosynthesis reveals the existence of multiple new intermediates and branching pathways and enables the identification of factors that contribute to the low levels of the natural product in the native producer.
  • Posted in Nat Chem Biol, Publications
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Fast bioelectrical switches

January 14th, 2019 by Michaela TerAvest

Fast bioelectrical switches

Fast bioelectrical switches, Published online: 14 January 2019; doi:10.1038/s41589-018-0212-3

Faster-than-transcription control of cellular activities is an important but challenging engineering target. Using split ferredoxins and induced dimerization or conformational changes, newly developed metalloprotein switches provide a fast method to control electron flux.

A chemical–genetic screen identifies ABHD12 as an oxidized-phosphatidylserine lipase

January 14th, 2019 by Dhanashree S. Kelkar

A chemical–genetic screen identifies ABHD12 as an oxidized-phosphatidylserine lipase

A chemical–genetic screen identifies ABHD12 as an oxidized-phosphatidylserine lipase, Published online: 14 January 2019; doi:10.1038/s41589-018-0195-0

Screening with a small-molecule reactive-oxygen-species generator identifies the serine hydrolase enzyme ABHD12 as a lipase for the proapoptotic oxidized phoshatidylserine (ox-PS) lipids, which trigger production of proinflammatory cytokines.
  • Posted in Nat Chem Biol, Publications
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[ASAP] Metabolic Engineering of <italic toggle=”yes”>Saccharomyces cerevisiae</italic> for Production of Shinorine, a Sunscreen Material, from Xylose

January 10th, 2019 by Seong-Hee Park, Kyusung Lee, Jae Woo Jang, Ji-Sook Hahn

TOC Graphic

ACS Synthetic Biology
DOI: 10.1021/acssynbio.8b00388
  • Posted in ACS Synthetic Biology, Publications
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[ASAP] Biological Engineered Living Materials: Growing Functional Materials with Genetically Programmable Properties

January 9th, 2019 by Charlie Gilbert, Tom Ellis

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ACS Synthetic Biology
DOI: 10.1021/acssynbio.8b00423
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[ASAP] Effector-Binding-Directed Dimerization and Dynamic Communication between Allosteric Sites of Ribonucleotide Reductase

January 8th, 2019 by Bill Pham, Richard J. Lindsay, Tongye Shen

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Biochemistry
DOI: 10.1021/acs.biochem.8b01131

A stable tetramer is not the only oligomeric state that mitochondrial single-stranded DNA binding proteins can adopt. [DNA and Chromosomes]

January 7th, 2019 by Saurabh P Singh, Vandna Kukshal, Roberto Galletto

Mitochondrial single-stranded DNA binding proteins (mtSSBs) are required for mitochondrial DNA replication and stability and are generally assumed to form homo-tetramers, and this species is proposed to be the one active for ssDNA binding. However, we recently reported that the mtSSB from Saccharomyces cerevisiae (ScRim1) forms homo-tetramers at high protein concentrations, whereas at low protein concentrations, it dissociates into dimers that bind ssDNA with high affinity . In this work, using a combination of analytical ultracentrifugation techniques and DNA binding experiments with fluorescently labeled DNA oligonucleotides, we tested whether the ability of ScRim1 to form dimers is unique among mtSSBs. Whereas human mtSSBs and those from Schizosaccharomyces pombe, Xenopus laevis and Xenopus tropicalis formed stable homo-tetramers, the mtSSBs from Candida albicans and Candida parapsilosis formed stable homo-dimers. Moreover, the mtSSBs from Candida nivariensis and Candida castellii formed tetramers at high protein concentrations, whereas at low protein concentrations they formed dimers, as did ScRim1. Mutational studies revealed that the ability to form either stable tetramers or dimers depended on a complex interplay of more than one amino acid at the dimer dimer interface and the C-terminal unstructured tail. In conclusion, our findings indicate that mtSSBs can adopt different oligomeric states, ranging from stable tetramers to stable dimers, and suggest that a dimer of mtSSB may be a physiologically relevant species that binds to ssDNA in some yeast species.