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Proteomic mapping of dynamic changes in kinase signaling after drug treatment identifies that AURKA inhibition is required for drug sensitivity, representing a new co-targeting opportunity with PI3K, AKT, or mTOR inhibitors in breast cancer.
Efficient production of a simple carbapenem antibiotic in Escherichia coli is achieved by a combination of feedback-resistant enzymes for increased precursor biosynthesis and inhibition of fatty acid synthesis for tolerance toward the toxic product.
Synthetic microbial consortia were engineered as experimental models of bacterial interactions within ecosystems, and mathematical models of their behavior were used to design more complex microbial systems with additional interactions.
The membrane-bound enzyme CybB can directly oxidize superoxide to molecular oxygen and transfer the sequestered electrons to ubiquinone in vitro, providing a mechanism for superoxide scavenging distinct from that of superoxide dismutase.
A single-molecule approach combined with molecular dynamics simulations to examine the conformational dynamics of the Escherichia coli ABC transporter BtuCD defines a coordinated sequence of events leading to unidirectional transport.
A Rab11 FRET biosensor reveals a spatiotemporal interplay between Rab11 and PtdIns(3)P turnover during the removal of recycling cargo from the endosome.
Structural, biochemical and cellular studies reveal JMJD7 to be a Jumonji-C oxygenase that catalyzes (3S)-lysyl hydroxylation of the translation factor family of GTPases, DRG1 and DRG2.
The antibacterial microvionin contains two new lanthipeptide modifications, a triamino-dicarboxylic acid (avionin) and an N-terminal guanidino fatty acid, that lead to the establishment of the lipolanthine natural product class.
Aided by the solving of the structures of human NMT1 with substrate-mimicking peptides, mapping of human and Arabidopsis myristoylomes defines a myristoylation recognition motif and over 1,000 myristoylated protein targets.
Selectivity of ligand-induced protein degradation and dimerization is conferred by plastic interprotein contacts. Computational protein–protein docking reveals the underlying interprotein contacts to inform the design of a BRD4 selective degrader.
Copper contributes to regulating zebrafish rest–activity cycles through the locus coeruleus system by modulating the biosynthesis of norepinephrine; brain copper deficiency leads to lower levels of both synaptic norepinephrine and daytime activity.
Potent pan-Atg8 or GABARAP-selective inhibitory peptides derived from giant neuronal ankyrin-B and -G effectively block autophagy in cell cultures and in C. elegans spatiotemporally.
Functional and structural characterization of PtmA2 reveals that it is an unusual non-adenylating acyl-CoA ligase and part of a system wherein the canonical acyl-CoA ligase reaction is separated into two half-reactions performed by distinct enzymes.
A bioinformatic strategy beginning with solute-binding proteins involved in sugar transport led to the functional annotation of four previously unknown catabolic pathways of the branched pentose d-apiose.
Although the conversion of (7S)-salutaridinol 7-O-acetate to thebaine can occur spontaneously, the identification of a thebaine synthase enzyme that catalyzes the reaction indicates how nature avoids the formation of labile hydroxylated byproducts.
Computational protein design, without subsequent directed evolution, rapidly provides a set of aspartase variants capable of biocatalytic asymmetric addition of ammonia to substituted acrylates, producing various enantiopure β-amino acids.
A genome-wide uracil profiling technology (termed “dU-seq”), based on selective labeling and biotin pull-down, reveals that uracil is enriched at the centromere of the human genome.
ABP profiling identifies uncharacterized S. aureus serine hydrolases, including the surface-localized FphB, which processes lipid ester substrates and is required for infection in vivo. An FphB inhibitor reduces in vivo bacterial load.
Combination of single-molecule tracking experiments and machine-learning approaches to monitor diffusional state transitions between ribosome-bound and free tRNAs allows codon resolution measurements of translation kinetics.
The structure of a monotopic polyprenol phosphate phosphoglycosyl transferase, PglC, reveals how it interacts with the bacterial membrane and coordinates a reaction between membrane-embedded and soluble substrates during glycoconjugate assembly.