Chemical biology articles within Nature Communications

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  • Article |

    A major proapoptotic mediator, Bax, is expressed in lung cancer and its activity can be regulated by phosphorylation. Here, the authors screen a library of compounds for their ability to alter the phosphorylation status of Bax and identify therapeutic candidates.

    • Meiguo Xin
    • , Rui Li
    •  & Xingming Deng

  • Article |

    The mechanism by which the common antibiotic streptomycin enters bacterial cells is unclear. Here, Iscla et al.show that streptomycin alters the activity of the bacterial mechanosensitive ion channel, MscL, inducing potassium efflux, and suggest that this channel may provide a route for cell entry.

    • Irene Iscla
    • , Robin Wray
    •  & Paul Blount

  • Review Article |

    The chemical modification of proteins is an important tool for probing natural systems and synthesizing novel conjugates. Here, Spicer and Davis review the merits and limitations of the most useful methods for selective modification at both natural and unnatural amino acids.

    • Christopher D. Spicer
    •  & Benjamin G. Davis

  • Article |

    Clozapine-induced agranulocytosis/granulocytopenia, or CIAG, is characterised by a rare and potentially fatal reaction to antipsychotic drugs. Here, the authors identify genetic variants in two immune-related genes that may contribute to the pathophysiology of CIAG.

    • Jacqueline I. Goldstein
    • , L. Fredrik Jarskog
    •  & Patrick F. Sullivan

  • Article |

    Cysteine S-sulphenylation provides redox regulation of protein functions, but the extent of this post-translational modification in cells is unknown. Here, Yang et al. develop a method to detect hundreds of S-sulphenylation sites in cells, and show that many of them respond to a physiologically relevant redox stimulus.

    • Jing Yang
    • , Vinayak Gupta
    •  & Daniel C. Liebler

  • Article |

    Following myocardial infarction, patients are at risk for reperfusion-induced ventricular fibrillation, a life-threatening condition. Here, Liang et al. show that the known ventricular fibrillation preventive effects of carbon monoxide are mediated through the inhibition of a subset of inward-rectifying potassium channels.

    • Shenghui Liang
    • , Quanyi Wang
    •  & Yuchun Gu

  • Article |

    Secondary multidrug transporters use ion concentration gradients to power the removal of drug molecules from cells. Here, Fluman et al. demonstrate that the bacterial transporter MdfA can catalyse the efflux of divalent cations in two consecutive transport cycles where each charged moiety is transported as if it were a separate substrate.

    • Nir Fluman
    • , Julia Adler
    •  & Eitan Bibi

  • Article
    | Open Access

    The advancement of sensitive, accurate and non-invasive methods to identify the allergen that drives allergic disease in an individual remains a challenge. Here, the authors develop a synthetic biology approach using human designer cells to profile allergic reactions against an array of allergens measuring histamine release from whole blood.

    • David Ausländer
    • , Benjamin Eggerschwiler
    •  & Martin Fussenegger

  • Article
    | Open Access

    Glucose transporters are a medically important class of membrane proteins often deregulated in diseases such as Type 2 diabetes. Here, Wisedchaisri et al. report the crystal structure of XylE in an inward-facing open conformation to provide a general mechanism of substrate transport for the sugar porter family of proteins.

    • Goragot Wisedchaisri
    • , Min-Sun Park
    •  & Tamir Gonen

  • Article
    | Open Access

    The GABAA receptor has an important role in brain function. Here Mortenson et al. design and synthesize photoactivatable compounds based on the GABAAantagonist gabazine and show that these can be used to inactivate the receptor, to identify new residues at the GABA binding site and can be adapted for trafficking studies.

    • Martin Mortensen
    • , Favaad Iqbal
    •  & Trevor G. Smart

  • Article
    | Open Access

    Identifying the site where a protein binds to another molecule is an important factor for the design of therapeutics intended to prevent this interaction. Here, the authors coat protein–receptor complexes with surface-binding molecules, and determine their interacting regions using mass spectrometry.

    • Alessandra Luchini
    • , Virginia Espina
    •  & Lance A. Liotta

  • Article |

    Certain bacterial metabolites can affect insect behaviour, but the underlying mechanisms are unclear. Here, the authors show that 2-aminoacetophenone, produced by the opportunistic human pathogen Pseudomonas aeruginosa, attracts flies and facilitates microbial dissemination and colonization of the fly gut.

    • Stefania-Elisavet Kapsetaki
    • , Ilias Tzelepis
    •  & Yiorgos Apidianakis

  • Article |

    Overexpression of a drug’s molecular target increases drug resistance in some cases. Here the authors show that overexpressing antibiotic targets in Escherichia colican cause positive and negative changes in drug resistance, depending on whether the drug induces harmful reactions involving its target.

    • Adam C. Palmer
    •  & Roy Kishony

  • Article
    | Open Access

    Cytidine-diphosphate diacylglycerol (CDP-DAG) is a central liponucleotide intermediate required for the biosynthesis of some phospholipids and is synthesized by CDP-DAG synthetase (Cds). Here, Liu et al. report the structure of a Cds that shows how it can accept hydrophilic and hydrophobic substrates, and suggest a mechanism that requires two metal ions.

    • Xiuying Liu
    • , Yan Yin
    •  & Zhenfeng Liu

  • Article |

    Unravelling the relationships between disease symptoms and underlying molecular origins is an important task in biomedical research. Here, Zhou et al.link diseases via their symptom overlap, and show that similar phenotypes are mirrored in networks that connect diseases with common genes or protein interactions.

    • XueZhong Zhou
    • , Jörg Menche
    •  & Amitabh Sharma

  • Article |

    In vitro biochemical pathways could provide the high yields required for economical commodity chemical production, but require circuitry development to regulate high-energy cofactors. Here, the authors design and test a simple purge valve system to maintain NADP+/NADPH balance in E. coli.

    • Paul H. Opgenorth
    • , Tyler P. Korman
    •  & James U. Bowie

  • Article
    | Open Access

    Focal epilepsy is difficult to treat with currently available drugs or surgical approaches. Kätzel et al.express mutant inhibitory receptors in the brains of rats with focal epilepsy and selectively activate these receptors by an exogenous compound, which results in region- and time-specific suppression of focal seizures

    • Dennis Kätzel
    • , Elizabeth Nicholson
    •  & Dimitri M. Kullmann

  • Article |

    Aldehyde dehydrogenase (ALDH)-expressing stem cells can be stained and sorted using a green fluorescent substrate. Minn et al.synthesise a red-shifted fluorescent ALDH probe and demonstrate sorting and microscopic staining of cells in the presence of a green fluorescent marker.

    • Il Minn
    • , Haofan Wang
    •  & Martin G. Pomper

  • Article
    | Open Access

    The (seco)iridoids and their monoterpenoid indole alkaloid (MIA) derivatives are plant-derived compounds with pharmaceutical applications. Here, the authors identify the last four missing steps of the (seco)iridoid pathway, which they reconstitute in an alternative plant host to produce the complex MIA, strictosidine.

    • Karel Miettinen
    • , Lemeng Dong
    •  & Danièle Werck-Reichhart

  • Article |

    The nuclear receptor PPARγ regulates insulin sensitivity and is the molecular target of anti-diabetic drugs. Here, Hughes et al. show demonstrate binding of synthetic PPARγ agonists to a previously unknown binding site within PPARγ and show this affects structure and function of the receptor.

    • Travis S. Hughes
    • , Pankaj Kumar Giri
    •  & Douglas J. Kojetin

  • Article
    | Open Access

    Ruthenium-cymene-based compounds are investigated as potential anticancer drugs. Here, Adhireksan et al.study two ruthenium-containing compounds with varying cytotoxicity and show that differences in ligand structure may explain their activity and binding to different subcellular targets.

    • Zenita Adhireksan
    • , Gabriela E. Davey
    •  & Curt A. Davey

  • Article |

    PDZ domains facilitate numerous protein-binding interactions, and their prevalence in the human genome has led to their investigation as drug targets. Here, the authors generate semisynthetic PDZ domains containing backbone mutations for the identification of important ligand-binding interactions.

    • Søren W. Pedersen
    • , Stine B. Pedersen
    •  & Kristian Strømgaard

  • Article
    | Open Access

    Aminoglycoside antibiotics target the ribosome but their limited selectivity for the bacterial ribosome can cause side effects in humans. Here, the authors synthesize 4′-O-ether or 4′,6′-O-acetal modifications and show that these compounds possess increased selectivity against bacterial ribosomes.

    • Déborah Perez-Fernandez
    • , Dmitri Shcherbakov
    •  & Erik C. Böttger

  • Article |

    Incomplete oxidation of fuels is a common problem in enzymatic fuel cells and it leads to low energy densities. Zhu et al. report the complete oxidation of sugar in an enzymatic fuel cell through a synthetic enzymatic pathway, which exhibits higher energy densities than lithium-ion batteries.

    • Zhiguang Zhu
    • , Tsz Kin Tam
    •  & Y. -H. Percival Zhang

  • Article |

    Opioid analgesic drugs act at opioid receptors to exert analgesic effects, but they also exert adverse side effects. In this study, the authors show that the TREK-1 potassium channel is responsible for mediating the analgesic effects of morphine but not the adverse side effects.

    • Maïly Devilliers
    • , Jérôme Busserolles
    •  & Alain Eschalier

  • Article |

    Plants primarily synthesize phenylalanine in plastids via arogenate. Here, Yoo et al. provide evidence that petunia flowers also employ an alternative microbial-like pathway to synthesize phenylalanine that is partially localized in the cytosol and interconnected with tyrosine catabolism.

    • Heejin Yoo
    • , Joshua R. Widhalm
    •  & Natalia Dudareva

  • Article
    | Open Access

    Chemical communication can evolve from compounds used for other purposes, but experimental evidence is scarce. Here, Weiss et al.show a gradual evolution of a defensive compound into a competition avoidance mediator and a sex pheromone, which was accompanied by diversification of chemical messengers to obtain the required specificity.

    • Ingmar Weiss
    • , Thomas Rössler
    •  & Johannes Stökl

  • Article |

    As drug-resistant strains of Mycobacterium tuberculosis continue to emerge, antitubercular drugs with novel mechanisms of action are in high demand. Here, the authors show that ebselen is an inhibitor of M. tuberculosisantigen 85 and reveal the mechanism of inhibition.

    • Lorenza Favrot
    • , Anna E. Grzegorzewicz
    •  & Donald R. Ronning

  • Article |

    Detailed knowledge of the water environment within proteins may lead to an increased understanding of protein folding and function. Here the authors present a tryptophan analogue with remarkable water catalysed proton-transfer properties that may be exploited for site-specific water sensing.

    • Jiun-Yi Shen
    • , Wei-Chih Chao
    •  & Pi-Tai Chou

  • Article
    | Open Access

    Membranes allowing transfer of a gas between a liquid and gas layer have applications in areas such as blood oxygenation and carbon dioxide capture. Here, a super liquid repellent membrane is fabricated, allowing high gas transfer and also avoiding wetting and clogging of the membrane pores.

    • Maxime Paven
    • , Periklis Papadopoulos
    •  & Hans-Jürgen Butt

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