Fueled by light

April 16th, 2018 by Grant Miura

Fueled by light

Fueled by light, Published online: 16 April 2018; doi:10.1038/s41589-018-0048-x

Fueled by light

Genome-wide mutant profiling predicts the mechanism of a Lipid II binding antibiotic

April 16th, 2018 by Marina Santiago

Genome-wide mutant profiling predicts the mechanism of a Lipid II binding antibiotic

Genome-wide mutant profiling predicts the mechanism of a Lipid II binding antibiotic, Published online: 16 April 2018; doi:10.1038/s41589-018-0041-4

Use of a combined Tn-seq and machine-learning approach for predicting mechanisms and targets of antibiotic action in Staphylococcus aureus shows that the natural product lysocin E (LysE) binds Lipid II on the cell surface and damages the membrane.
  • Posted in Nat Chem Biol, Publications
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Spotting the signal

April 16th, 2018 by Caitlin Deane

Spotting the signal

Spotting the signal, Published online: 16 April 2018; doi:10.1038/s41589-018-0047-y

Spotting the signal

[ASAP] Second-Shell Hydrogen Bond Impacts Transition-State Structure in <italic toggle=”yes”>Bacillus subtilis</italic> Oxalate Decarboxylase

April 11th, 2018 by Wen Zhu, Laurie A. Reinhardt, Nigel G. J. Richards

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.8b00214

Author Correction: Mitochondrial DNA repair and replication proteins revealed by targeted chemical probes

April 2nd, 2018 by Simon Wisnovsky

Author Correction: Mitochondrial DNA repair and replication proteins revealed by targeted chemical probes

Author Correction: Mitochondrial DNA repair and replication proteins revealed by targeted chemical probes, Published online: 20 August 2018; doi:10.1038/s41589-018-0040-5

Author Correction: Mitochondrial DNA repair and replication proteins revealed by targeted chemical probes
  • Posted in Nat Chem Biol, Publications
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The structural organization of substrate loading in iterative polyketide synthases

April 2nd, 2018 by Dominik A. Herbst

The structural organization of substrate loading in iterative polyketide synthases

The structural organization of substrate loading in iterative polyketide synthases, Published online: 02 April 2018; doi:10.1038/s41589-018-0026-3

The crystal structure and cryo-electron microscopy of the loading/condensing region of a nonreducing polyketide synthase reveals the insertion of a starter-unit acyltransferase into the condensing region and an asymmetrical post-loading state.
  • Posted in Nat Chem Biol, Publications
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Super-long single-molecule tracking reveals dynamic-anchorage-induced integrin function

April 2nd, 2018 by Taka A. Tsunoyama

Super-long single-molecule tracking reveals dynamic-anchorage-induced integrin function

Super-long single-molecule tracking reveals dynamic-anchorage-induced integrin function, Published online: 02 April 2018; doi:10.1038/s41589-018-0032-5

Dissolved oxygen and a reducing-plus-oxidizing system suppress photobleaching and photoblinking in single-molecule tracking experiments, allowing long recordings of CD47 and integrin that showed temporary immobilization within focal adhesions.
  • Posted in Nat Chem Biol, Publications
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FINO<sub>2</sub> initiates ferroptosis through GPX4 inactivation and iron oxidation

April 2nd, 2018 by Michael M. Gaschler

FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation

FINO<sub>2</sub> initiates ferroptosis through GPX4 inactivation and iron oxidation, Published online: 02 April 2018; doi:10.1038/s41589-018-0031-6

FINO2 is a small molecule that requires the endoperoxide moiety and hydroxyl group to promote ferroptosis through indirect inhibition of GPX4 enzymatic function and direct oxidation of iron, resulting in increased lipid peroxidation.
  • Posted in Nat Chem Biol, Publications
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[ASAP] Structural Determinants for the Interactions of Chemically Modified Nucleic Acids with the Stabilin-2 Clearance Receptor

March 29th, 2018 by Hans Gaus, Colton M. Miller, Punit P. Seth, Edward N. Harris

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.8b00126

Effects of hypo O-GlcNAcylation on Drosophila development [Developmental Biology]

March 27th, 2018 by Daniel N Mariappa, Andrew Ferenbach, Daan M.F. van Aalten

Post-translational modification of serine/threonine residues in nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAcylation) is an essential regulatory mechanism in many cellular processes. In Drosophila, null mutants of the polycomb gene O-GlcNAc transferase (OGT, also known as super sex combs [sxc]) display homeotic phenotypes. To dissect the requirement for O-GlcNAc signaling in Drosophila development, we used CRISPR/Cas9 gene editing to generate rationally designed sxc catalytically hypomorphic or null point mutants. Of the fertile males derived from embryos injected with the CRISPR/Cas9 reagents, 25% produced progeny carrying precise point mutations with no detectable off-target effects. One of these mutants, the catalytically inactive sxcK872M, was recessive lethal, whereas a second mutant, the hypomorphic sxcH537A, was homozygous viable. We observed that reduced total protein O-GlcNAcylation in the sxcH537A mutant is associated with a wing vein phenotype and temperature-dependent lethality. Genetic interaction between sxcH537A and a null allele of Drosophila host cell factor (dHcf), encoding an extensively O-GlcNAcylated transcriptional coactivator, resulted in abnormal scutellar bristle numbers. A similar phenotype was also observed in sxcH537A flies lacking a copy of skuld (skd), a Mediator complex gene known to affect scutellar bristle formation. Interestingly, this phenotype was independent of OGT Polycomb function or dHcf downstream targets. In conclusion, the generation of the endogenous OGT hypomorphic mutant sxcH537A enabled us to identify pleiotropic effects of globally reduced protein O-GlcNAc during Drosophila development. The mutants generated and phenotypes observed in this study provide a platform for discovery of OGT substrates that are critical for Drosophila development.