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Targeting the host during antibiotic discovery efforts is a viable strategy, and the approach has benefited from phenotypic screening of model organisms such as worms, zebrafish, and mice.
The discovery of cytochrome P450 monooxygenases that catalyze oxidative demethylation of 6-O-methyl-D-galactose reveals a new activity of cytochrome P450 enzymes and their role in polysaccharide biomass degradation in marine bacteria.
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The structure of a Stig cyclase, HpiC1, reveals how it catalyzes Cope rearrangement and 6-exo-trig cyclization, including how it controls the position of electrophilic aromatic substation that distinguishes hapalindole from fischerindole alkaloids.
Directed evolution of opsins via robotic high-content screening finds a fluorescent reporter of voltage that is simultaneously optimized for brightness, localization and voltage sensitivity and is applicable in three model systems.
Directed evolution of Trp repressor (TrpR) variants that are responsive to halogenated tryptophan analogs and recognize new operator sites serve as useful components for constructing complex gene expression networks.
The crystal structure of EarP, an inverting glycosyltransferase that generates rhamnosyl-arginine modifications, suggests that the enzyme uses an SN2 reaction mechanism that may involve perturbation of the donor sugar nucleotide conformation.
The substrate-tolerant lanthipeptide synthetase ProcM enables the construction of a plasmid-encoded library of bicyclic lanthipeptides, from which an inhibitor of the p6–UEV protein–protein interaction is identified by a reverse two-hybrid screen.
Networking-associated genome mining on bacterial genomes followed by chemical and enzymatic analysis identified a mechanism of resistance toward nonribosomal peptide antibiotics based on hydrolytic cleavage by d-stereospecific peptidases.
A nonequilibrium thermodynamic model can explain how molecular chaperones such as GroEL can use the energy from ATP hydrolysis to maintain substrate proteins in an active state, even under conditions that favor the substrate's inactive unfolded state.
A photoswitchable diacylglycerol enabled a screen that found critical TRPC3 lipid-sensing residues and identified a lateral fenestration in the pore domain that allows lipids to protrude into the permeation pathway to control channel gating.
Selective TRIM24 degradation is achieved by co-opting the VHL E3 ubiquitin ligase machinery. TRIM24 degradation outperforms bromodomain inhibition, with an enhanced antiproliferative effect in acute leukemia, a novel context of TRIM24 dependency.
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