News & Comment

  • News & Views |

    The electrogenic bacterium Geobacter synthesizes conductive extracellular nanowires to facilitate electron transfer that powers respiration. A highly conductive form of these nanowires is now revealed to be composed of oligomers of an 8-heme cytochrome, OmcZ.

    • Thomas A. Clarke
    •  & Marcus J. Edwards
  • News & Views |

    Coherent Raman imaging enables mapping of chemical features at subcellular resolution, setting the stage for tracking lipids and other metabolites in intact living systems.

    • Bennett W. Fox
    •  & Frank C. Schroeder
  • News & Views |

    Bariatric surgery causes high rates of remission of type 2 diabetes; however, the mechanisms remain unresolved. A new study identifies cholic-acid-7-sulfate as a novel contributor to the metabolic benefits of bariatric surgery and an attractive target for treatment of type 2 diabetes.

    • Bethany P. Cummings
  • News & Views |

    It is generally believed that large protein complexes provide a catalytic advantage due to substrate channeling between enzymatic domains. However, the structure and function of the pentafunctional AROM complex suggests a noteworthy exception.

    • Martin St. Maurice
  • News & Views |

    Reprogramming requires resetting the epigenome toward a pluripotent chromatin state. A new chemical screen identifies epigenetic and signaling roadblocks for reprogramming of human somatic cells, with the inhibition of these roadblocks resulting in a more permissive epigenome for reprogramming.

    • Maximilian W. D. Raas
    • , Dick W. Zijlmans
    •  & Hendrik Marks
  • News & Views |

    Altered glycosylation helps cancer cells evade immune destruction, and targeted remodeling of glycans in vivo offers the ability to reprogram immune responses. A stable chemical linkage between an antibody and neuraminidase enables the targeted destruction of self-associated sialic acids to enhance antitumor immunity.

    • Emily Rodrigues
    •  & Matthew S. Macauley
  • News & Views |

    Two recent studies identified CDK12 inhibitors that bind to CDK12–cyclin K complexes and act as molecular glues to stabilize an interaction with the ubiquitin ligase CUL4–DDB1, leading to cyclin K degradation.

    • Willem den Besten
    •  & J. Russell Lipford
  • News & Views |

    Thermodynamic principles are used to map the phase behavior of a tunable protein-binding system under crowded cellular conditions. This study marks a substantial step forward in relating molecular interactions to material properties and cellular processes involving protein self-assembly.

    • Roshan Mammen Regy
    •  & Jeetain Mittal
  • News & Views |

    A new molecule that specifically activates a key protein homeostasis pathway has been identified. The ability to initiate the IRE1–XBP1s branch of the unfolded protein response opens up new avenues for basic research and treatment of disease.

    • Nadia Cummins
    •  & Rebecca C. Taylor
  • News & Views |

    Rho family GTPases regulate cell behaviors through complex signaling networks that act on rapid timescales in subcellular spatial domains. New live-cell biosensors and analytical methods now provide critical tools to dissect Rho GTPase regulation and to better understand cellular information processing.

    • Dean E. Natwick
    •  & Sean R. Collins
  • News & Views |

    An NMR method to monitor conformational states of challenging large protein targets is described. The method, which can be used to evaluate distances between two labels and to measure conformational exchange rates, revealed an unanticipated outward-facing state in a glutamate transporter.

    • Ricky C. Cheng
    •  & Merritt Maduke
  • News & Views |

    Molecular glues induce novel protein–protein interactions to modulate protein function and downstream biology. A recent study unveils manumycin polyketides with multiple electrophilic centers as covalent molecular glues between UBR7 and TP53.

    • Zhi Zeng
    •  & Ting Han
  • News & Views |

    The enzyme 5-lipoxygenase (5-LOX) initiates the biosynthesis of leukotrienes (LT), potent mediators of the inflammatory response. The first crystal structures of two complexes of inhibitor bound to 5-LOX reveal the functional consequences of the binding, including a change in the regiospecificity toward a 12/15-lipoxygenating enzyme.

    • Homero Rubbo
    •  & Irene Wood
  • News & Views |

    Glucose 6-phosphate dehydrogenase (G6PD) stands at the head of the pentose phosphate pathway, which is responsible for nucleotide synthesis. The identification and thorough validation of an improved G6PD inhibitor provide a valuable new tool compound for studying metabolism.

    • Michael E. Pacold
  • News & Views |

    A suite of new enzymes reveals more on how Nature breaks down plant-based polysaccharides and how these enzymes might be harnessed in the utilization of plant-based biomass.

    • Paul H. Walton
  • News & Views |

    A new study reveals that, in addition to its longstanding role in recruiting proteins to the proteasome, ubiquitination can also induce a structural destabilization that allows the target protein to be efficiently unraveled for degradation.

    • Cameron G. Roberts
    •  & Jonathan N. Pruneda
  • Obituary |

    Rolf Huisgen left us on 26 March 2020, just three months shy of his 100th birthday. His work has had an enormous influence on chemical biology, ranging from new methods for the synthesis of chemical probes to “click chemistry” and its application to in vivo bioconjugation.

    • Dirk Trauner
  • Feature |

    We present a selection of papers published in Nature Chemical Biology over the past five years that reflect the diversity and excitement of chemical biology research.

  • Feature |

    We asked a collection of chemical biologists, “What was the most exciting research achievement or technology innovation in chemical biology in the last five years?” and reveal some of the perspectives we received.

  • Editorial |

    Over the past decade and a half, chemical biology has crystallized as a discipline and extended its reach into new scientific areas, but the field’s greatest promise lies ahead.

  • News & Views |

    The discovery of selective modulators of two Cryptochrome isoforms, CRY1 and CRY2, permits a deeper understanding of how circadian clock proteins impact diverse aspects of our daily 24-h rhythms and how this intersects with metabolic pathways relevant to disease.

    • Julia Lara
    •  & Brian D. Zoltowski
  • News & Views |

    A pair of fluorescent indicator-tagged DNA-duplex scaffolds permit assessments of nitric oxide (NO) production on cell surfaces and in intracellular networks. The application of these nanoprobes indicates formations of local NO signals that might conserve cancer cell integrity.

    • Emrah Eroglu
    • , Thomas Michel
    • , Wolfgang F. Graier
    •  & Roland Malli
  • News & Views |

    A combination of biochemical and biophysical techniques to document the asymmetric distribution of lipids, with a particular focus on the acyl tails, in mammalian cell membranes show that protein transmembrane domains are similarly asymmetric.

    • Maria Makarova
    •  & Dylan M. Owen
  • News & Views |

    Oxygen activation mechanisms catalyzed by flavin cofactors are established for electron transfer (oxidases) and C4a covalent flavin–oxygen adduct formation (oxygen-inserting monooxygenases). A new paradigm for oxygen insertion involving a flavin-N5-aminoperoxide intermediate has now been discovered in select flavin-dependent monooxygenases.

    • David Leys
    •  & Nigel S. Scrutton
  • News & Views |

    Emergence of drug resistance limits the efficacy of HIV drugs, which currently requires life-long administration. In vitro high-throughput screening for competition with a broadly neutralizing antibody of HIV identified a small molecule that extends the strategies for targeting HIV.

    • Shan Su
    •  & Shibo Jiang
  • News & Views |

    The biological function and origin of m6A in DNA have been widely debated. A new study demonstrates that the majority of m6A in DNA originates from RNA catabolism via a nucleotide salvage pathway.

    • Paolo Spingardi
    •  & Skirmantas Kriaucionis
  • News & Views |

    Using new letters of DNA to encode information promises to expand the genetic code in a transformative way. A new semisynthetic organism has been created that uses 67 codons for protein biosynthesis, with three new codons based on unnatural nucleotides.

    • Michael C. Jewett
    •  & Michael J. Hammerling
  • News & Views |

    Ferroptosis induced by GPX4 inhibition offers promise for killing drug-resistant cancer cells, yet current GPX4 inhibitors lack selectivity. The discovery of masked nitrile oxide electrophiles as selective prodrug inhibitors of GPX4 points to an attractive path for chemically inducing ferroptosis.

    • Stefan G. Kathman
    •  & Benjamin F. Cravatt
  • Research Highlight |

    • Yiyun Song