Chemical biology articles within Nature

Featured

  • Research Briefing |

    A broadly applicable method allows selective, rapid and efficient chemical modification of the side chain of tryptophan amino acids in proteins. This platform enables systematic, proteome-wide identification of tryptophan residues, which can form a bond (called cation–π interaction) with positively charged molecules. Such interactions are key in many biochemical processes, including protein-mediated phase separation.

  • Article |

    VVD-133214, a clinical-stage, covalent allosteric inhibitor of the helicase WRN, was well tolerated in mice and led to robust tumour regression in multiple microsatellite-instability-high colorectal cancer cell lines and patient-derived xenograft models.

    • Kristen A. Baltgalvis
    • , Kelsey N. Lamb
    •  & Todd M. Kinsella

  • Article |

    Monoamines and neurotoxicants share a binding pocket in VMAT1 featuring polar sites for specificity and a wrist-and-fist shape for versatility, and monoamine enrichment in storage vesicles arises from dominant import via favoured lumenal-open transition of VMAT1 and protonation-precluded binding during its cytoplasmic-open transition.

    • Jin Ye
    • , Huaping Chen
    •  & Weikai Li

  • News & Views |

    In experiments dubbed the Random Genome Project, researchers have integrated DNA strands with random sequences into yeast and mouse cells to find the default transcriptional state of their genomes.

    • Sean R. Eddy

  • Article |

    Global profiling of hyper-reactive tryptophan sites across whole proteomes using tryptophan chemical ligation by cyclization (Trp-CLiC) reveals a systematic map of tryptophan residues that participate in cation–π interactions, including functional sites that can regulate protein-mediated phase-separation processes.

    • Xiao Xie
    • , Patrick J. Moon
    •  & Christopher J. Chang

  • Article
    | Open Access

    A multidimensional proteomics analysis of the interactions between around 2,000 nuclear proteins and over 80 modified dinucleosomes representing promoter, enhancer and heterochromatin states provides insights into how chromatin states are decoded by chromatin readers.

    • Saulius Lukauskas
    • , Andrey Tvardovskiy
    •  & Till Bartke

  • Article
    | Open Access

    Studies using genetic screening, biophysical characterization and structural reconstitution elucidate the mechanism of action and enable rational design of a new class of functional compounds that glue target proteins to E3 ligases via intramolecularly bridging two domains to enhance intrinsic protein–protein interactions and promote target ubiquitination and degradation.

    • Oliver Hsia
    • , Matthias Hinterndorfer
    •  & Alessio Ciulli

  • Research Briefing |

    Public repositories of metabolomics data are expanding rapidly and can be leveraged to uncover previously undescribed metabolites. Reverse metabolomics is a workflow in which thousands of small compounds are synthesized using combinatorial chemistry, and their molecular ‘fingerprints’ are then used to discover where they are localized in tissues and biological fluids and how they are associated with health and disease in humans.

  • Article
    | Open Access

    tRNA display enables the direct selection of orthogonal aminoacyl-tRNA synthetases that acylate orthogonal tRNAs with non-canonical monomers, enabling in vivo synthesis of proteins that include these monomers and expanding the repertoire of the genetic code.

    • Daniel L. Dunkelmann
    • , Carlos Piedrafita
    •  & Jason W. Chin

  • Article
    | Open Access

    A mechanism of lipid transport inhibition has been identified for a class of peptide antibiotics effective against resistant Acinetobacter strains, which may have applications in the inhibition of other Gram-negative pathogens.

    • Karanbir S. Pahil
    • , Morgan S. A. Gilman
    •  & Daniel Kahne

  • Article |

    Enzyme-bound ketyl radicals derived from thiamine diphosphate are selectively generated through single-electron oxidation by a photoexcited organic dye and shown to lead to enantioselective radical acylation reactions.

    • Yuanyuan Xu
    • , Hongwei Chen
    •  & Xiaoqiang Huang

  • Article
    | Open Access

    A new discovery strategy, ‘reverse metabolomics’, facilitates high-throughput matching of mass spectrometry spectra in public untargeted metabolomics datasets, and a proof-of-concept experiment identified an association between microbial bile amidates and inflammatory bowel disease.

    • Emily C. Gentry
    • , Stephanie L. Collins
    •  & Pieter C. Dorrestein

  • Article |

    Cellular lysine residues can be both methylated and acetylated on the same sidechain to form Nε-acetyl-Nε-methyllysine (Kacme), which is found on histone H4 across a range of species and across mammalian tissues and is associated with active chromatin.

    • William J. Lu-Culligan
    • , Leah J. Connor
    •  & Matthew D. Simon

  • Article |

    A scalable total synthesis of portimines enables structural reassignment of portimine B and in-depth functional evaluation of portimine A, revealing that portimine A induces translation inhibition selectively in human cancer cells and is efficacious in vivo tumour-clearance models.

    • Junchen Tang
    • , Weichao Li
    •  & Phil S. Baran

  • News & Views |

    Molecules have been developed that switch a transcription factor from being a repressor of gene expression to an activator — and thereby able to kill cancer cells. The findings offer a fresh strategy for designing anticancer drugs.

    • James D. Phelan
    •  & Louis M. Staudt

  • Article |

    A biosensor comprising bacteria engineered to respond to transient inflammatory signals has been packaged with electronic readout and transmission circuits in a small device that could be swallowed to monitor gastrointestinal health.

    • M. E. Inda-Webb
    • , M. Jimenez
    •  & T. K. Lu

  • Article |

    A new class of molecules can recruit downstream transcription factors or endogenous cancer drivers to cell death promoters and activate the expression of these genes.

    • Sai Gourisankar
    • , Andrey Krokhotin
    •  & Gerald R. Crabtree

  • Article |

    X-ray crystallography and cryo-electron microscopy analyses of Lettuce—a DNA mimic of GFP—bound to various fluorophores reveal previously unknown structures of DNA that rival analogous RNAs in complexity.

    • Luiz F. M. Passalacqua
    • , Michael T. Banco
    •  & Adrian R. Ferré-D’Amaré

  • Research Briefing |

    A deep-learning model called Geneformer has been developed and pretrained using about 30 million single-cell gene-expression profiles to enable it to make predictions about gene-network biology in instances in which gene-expression data are limited. Geneformer can be tuned for many downstream applications to accelerate discovery of key gene-network regulators and candidate therapeutic targets.

  • Research Briefing |

    Nematode worms that parasitize plants ravage food crops and threaten global food security. Conventional nematode control relies on agrochemicals that are broadly toxic, so less-risky strategies are needed. Benign precursor chemicals that are metabolically converted to lethal products selectively in worm tissue could be the solution.

  • Article |

    A metabolically bioactivated selective imidazothiazole nematicide shows comparable effectiveness at controlling plant root infection by Meloidogyne incognita to commercial nematicides, which are traditionally nonselective and toxic.

    • Andrew R. Burns
    • , Rachel J. Baker
    •  & Peter J. Roy

  • Article
    | Open Access

    Active-state structures of the κ-opioid receptor in complexes with the G-protein heterotrimers Gi1, GoA, Gz and Gg provide insights into the actions of hallucinogenic opioids and G-protein-coupling specificity at the κ-opioid receptor.

    • Jianming Han
    • , Jingying Zhang
    •  & Tao Che

  • Research Briefing |

    Creating protein interactions through computational design is a key challenge in the fields of both basic and translational biology. An approach that uses the machine-learned fingerprints of protein-surface features was used to produce synthetic proteins that engage immunotherapeutic or viral targets with binding affinities comparable to those of naturally occurring proteins.

  • Article |

    By using in vivo ultrafast TA spectroscopy, extraction of electrons directly from photoexcited PSI and PSII in cyanobacterial cells using exogenous electron mediators is demonstrated.

    • Tomi K. Baikie
    • , Laura T. Wey
    •  & Jenny Z. Zhang

  • Nature Podcast |

    A streamlined genome makes bacteria immune to viral infection, and designing mini-MRI scanners for low- and middle-income countries.

    • Shamini Bundell
    •  & Nick Petrić Howe

  • Article |

    Through the use of cryo-electron microscopy and molecular dynamics stimulations, mechanistic insight into the binding of an odorant to the human odorant receptor OR51E2 is provided.

    • Christian B. Billesbølle
    • , Claire A. de March
    •  & Aashish Manglik

  • Article
    | Open Access

    Biochemical and molecular dynamics studies show that the third intracellular loop of G protein-coupled receptors autoregulates the receptor activity and tunes the signalling specificity by controlling access to the G protein-binding site.

    • Fredrik Sadler
    • , Ning Ma
    •  & Sivaraj Sivaramakrishnan

  • News & Views |

    The discovery of bacterial compounds that have antifungal properties opens up opportunities for the development of agents that protect crops from a devastating disease.

    • Andrew Mitchinson

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