Nature Chemical Biology

Target class drug discovery ()
Selection of molecular targets based on disease understanding is a dominant paradigm in drug discovery. We argue that a focus on classes of targets with central roles in biology provides a complimentary approach that has higher quality outcomes in early discovery efforts.
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Bioorthogonal chemistry: Click on, click off ()

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Chemical methods: DREADDs see no CNO ()

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Developmental signaling: Peaking early ()

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Protein engineering: Expanding splicing versatility ()

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Kinetochore regulation: Let there be light ()
Kinetochores form the critical interface with spindle microtubules that accounts for chromosome movement and segregation fidelity during mitosis. Spatial and temporal control of motor protein and checkpoint signaling at kinetochores is now possible with a new set of optogenetic tools.
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Biosynthesis: SAM cycles up for colibactin ()
The introduction of a cyclopropyl group is critical for imparting colibactin with the ability to cleave DNA. Nonribosomal peptide synthetase ClbH and polyketide synthase ClbI are now shown to work in concert to convert S-adenosylmethionine into this cyclopropyl group.
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Genome mining: Digging the tunnel for chemical space ()
Genome mining reveals a new ribosomally synthesized and post-translationally modified peptide (RiPP) from Klebsiella pneumoniae. This new antibiotic inhibits bacterial ribosomes by obstructing the peptide exit tunnel, and its modular nature presents a unique opportunity for future engineering of antibacterial drugs.
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Colibactin assembly line enzymes use S-adenosylmethionine to build a cyclopropane ring ()
Despite containing an α-amino acid, the versatile cofactor S-adenosylmethionine (SAM) is not a known building block for nonribosomal peptide synthetase (NRPS) assembly lines. Here we report an unusual NRPS module from colibactin biosynthesis that uses SAM for amide bond formation and subsequent cyclopropanation. Our findings showcase a new use for SAM and reveal a novel biosynthetic route to a functional group that likely mediates colibactin's genotoxicity.
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Molecular basis for the unusual ring reconstruction in fungal meroterpenoid biogenesis ()

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Modulating the DNA polymerase β reaction equilibrium to dissect the reverse reaction ()

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Bisphosphoglycerate mutase controls serine pathway flux via 3-phosphoglycerate ()

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A genetically encoded tool for manipulation of NADP+/NADPH in living cells ()

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Optogenetic control of kinetochore function ()

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Small-molecule studies identify CDK8 as a regulator of IL-10 in myeloid cells ()

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Metals induce transient folding and activation of the twister ribozyme ()

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Crystal structures of trimeric HIV envelope with entry inhibitors BMS-378806 and BMS-626529 ()

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Oxidative cleavage of polysaccharides by monocopper enzymes depends on H2O2 ()

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Klebsazolicin inhibits 70S ribosome by obstructing the peptide exit tunnel ()

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Erratum: A Vibrio cholerae autoinducer–receptor pair that controls biofilm formation ()

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Erratum: A Vibrio cholerae autoinducer–receptor pair that controls biofilm formation ()

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Corrigendum: Parallel evolution of non-homologous isofunctional enzymes in methionine biosynthesis ()

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