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Photorhabdus noenieputensis (a gut microbiota symbiont of nematodes) produces a macrocyclic antibiotic, evybactin, that selectively kills Mycobacterium tuberculosis (Mtb). The Mtb membrane transporter BacA imports evybactin into the cell, where it binds to DNA gyrase and causes cell death.
The microtubule-associated protein tau is strongly linked to Alzheimer’s disease, but the physiological functions of tau on microtubules remain unclear. New experiments reveal that tau recognizes and alters the conformation of the underlying microtubule lattice by forming envelopes that surround its surface, suggestive of a novel role for tau in cell physiology.
Evybactin is an antimicrobial natural product that targets DNA gyrase, where it binds to a site overlapping with synthetic thiophene poisons and exerts selectivity for Mycobacterium tuberculosis via its transport mechanism into the cell.
Microtubule-associated proteins tau and MAP2 cooperatively form protein envelopes that compact the underlying tubulin lattice, revealing a novel role for these proteins in altering microtubule structure.
Loss of myelin causes neurological symptoms for patients with multiple sclerosis. This Perspective details how phenotypic screening has accelerated discovery efforts toward potential ‘remyelinating therapeutics’.
The description of the cryo-EM structure of an orphan adhesion GPCR–Gs protein complex in apo state facilitates the screening and identification of potential ligands of ADGRG2.
Using structural and biochemical methods, Liang et al. revealed a C-terminal glutamine-end recognition mechanism of TRIM7 E3 ligases, which enables identification of substrates for TRIM7 and provides insight into the versatile functions of TRIM7 in viral infection and the C-degron pathway.
Metabolic labeling experiments on fermenting yeast revealed that ethanol is oxidized to acetaldehyde and acetyl-CoA and is also a major source of NADH and NADPH, demonstrating that ethanol can be consumed as a TCA cycle and redox fuel.
A chemical genomics approach was used to identify regulators of drug sensitivity for pyrvinium, a cytotoxic agent with anti-cancer potential, revealing mitochondrial complex I sensitivities and a role for C1orf115 in regulating ABCB1 activity.
Elucidating the interactions between serum protein-bound nanoparticles and cell-surface receptors typically operates on a per protein–receptor interaction basis. Integration of omic approaches for testing thousands of interactions unbiasedly reveals important interactions that drive cellular uptake of nanoparticles.
Bicyclostreptins are peptide natural products in which a macrocyclic β-ether and a heterocyclic sp3–sp3 linkage between a backbone amide nitrogen and an adjacent α-carbon are installed by two radical S-adenosylmethionine metalloenzymes.
A combination of mass spectrometry, pooled genome screens and STRING analysis identifies key uptake mediating interactions between nanoparticle-adsorbed proteins and cells via the low-density lipoprotein receptor.
Metabokiller is a novel, explainable AI-backed method for carcinogenicity prediction that leverages the biological and chemical properties associated with carcinogens.
Merging the generalized extracellular molecule sensor (GEMS) system with screening designed ankyrin repeat proteins (DARPins) identifies an advanced modular bispecific extracellular receptor (AMBER) for detection of fibrinogen degradation products.