Chemical biology articles within Nature Communications

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  • Article
    | Open Access

    Cofactor F420 plays crucial roles in bacterial and archaeal metabolism, but its biosynthetic pathway is not fully understood. Here, the authors present the structure of one of the enzymes and provide experimental evidence for a substantial revision of the pathway, including the identification of a new intermediate.

    • Ghader Bashiri
    • , James Antoney
    •  & Colin J. Jackson
  • Article
    | Open Access

    RNA sensors—Riboswitches—respond to the binding of small molecules ligands through structure modification. Here the authors identify synthetic small molecules that bind and regulate the activity of PreQ1 Riboswitches despite having no obvious chemical similarity to the cognate ligand.

    • Colleen M. Connelly
    • , Tomoyuki Numata
    •  & John S. Schneekloth Jr.
  • Article
    | Open Access

    Curaxins are a recently discovered class of anti-cancer agents that disturbs DNA/histone interactions within. Here the authors provide evidence that curaxins affect the spatial genome organization and compromise enhancer-promoter communication necessary for expression of several oncogenes, including MYC.

    • Omar L. Kantidze
    • , Artem V. Luzhin
    •  & Sergey V. Razin
  • Article
    | Open Access

    Protein kinase A (PKA) is typically activated by cAMP. Here, Bachmaier et al. show that PKA of Trypanosoma is activated by nucleoside-related ligands, explain the ligand selectivity swap by a co-crystal structure of trypanosome PKAR, and identify potential downstream targets by phosphoproteomics.

    • Sabine Bachmaier
    • , Yuri Volpato Santos
    •  & Michael Boshart
  • Article
    | Open Access

    Extracellular electron uptake (EEU) is the ability of microbes to take up electrons from solid-phase conductive substances such as metal oxides. Here, Guzman et al. show that electrons enter the photosynthetic electron transport chain and are used for CO2 fixation during EEU in a phototrophic bacterium.

    • Michael S. Guzman
    • , Karthikeyan Rengasamy
    •  & Arpita Bose
  • Article
    | Open Access

    Proteins continuously undergo non-enzymatic modifications such as glycation, which accumulate under physiological conditions but can be enhanced in disease. Here the authors characterise histone glycation, provide evidence that it affects chromatin, particularly in breast cancer, and identify DJ-1 as a deglycase.

    • Qingfei Zheng
    • , Nathaniel D. Omans
    •  & Yael David
  • Article
    | Open Access

    Super-resolution microscopy with spontaneously blinking dyes is dependent on pH and polarity of the medium. Here the authors introduce a photoactivatable fluxional fluorophore for live cell imaging that allows control over the fraction of spontaneously blinking molecules independently of medium properties.

    • Elias A. Halabi
    • , Dorothea Pinotsi
    •  & Pablo Rivera-Fuentes
  • Article
    | Open Access

    Combination therapy holds great promise, but discovery remains challenging. Here, the authors propose a method to identify efficacious drug combinations for specific diseases, and find that successful combinations tend to target separate neighbourhoods of the disease module in the human interactome.

    • Feixiong Cheng
    • , István A. Kovács
    •  & Albert-László Barabási
  • Article
    | Open Access

    Optical control over receptor tyrosine kinase (RTK) activity can find application in both basic biology and synthetic biology. Here the authors combine the photosensory module of DrBphP bacterial phytochrome with the Trk family of RTKs to obtain Trks that are reversibly switchable with near-infrared and far-red light.

    • Anna V. Leopold
    • , Konstantin G. Chernov
    •  & Vladislav V. Verkhusha
  • Article
    | Open Access

    Attempts to image activated macrophages in vivo have been hampered by selectivity and delivery problems. Here the authors develop a small molecule fluorescent probe specific to activated M1 and M2 macrophages, identify the orphan receptor Slc18b1/SLC18B1 as the mechanism of uptake, and use it to image atherosclerosis in mice.

    • Sung-Jin Park
    • , Beomsue Kim
    •  & Young-Tae Chang
  • Article
    | Open Access

    Amphihelical antimicrobial peptides (AMPs) are bactericidal host defense factors, but their function as immunomodulators is emerging. Here the authors show that several AMPs organize DNA into periodic nanocrystals by self-assembling into superhelical protofibril scaffolds, which potentiates DNA sensing by TLR9.

    • Ernest Y. Lee
    • , Changsheng Zhang
    •  & Gerard C. L. Wong
  • Article
    | Open Access

    Taxanes are natural products which bind beta-tubulin, stabilize microtubules and have a broad spectrum of anticancer activity. Here authors employ a computational binding site similarity screen and cell-based assays to reveal a SERM cross-reactivity between the estrogen receptor and the beta-tubulin taxane binding pocket.

    • Yu-Chen Lo
    • , Olga Cormier
    •  & Russ B. Altman
  • Article
    | Open Access

    The Pseudomonas putida toxin GraT and antitoxin GraA form a type II toxin-antoxin module. Here the authors present the crystal structures of the GraA dimer, GraTA and GraA-DNA complexes and show that GraT contains a functionally important N-terminal intrinsic disordered region that prevents the binding of the GraTA complex to the operator.

    • Ariel Talavera
    • , Hedvig Tamman
    •  & Remy Loris
  • Article
    | Open Access

    The tethered ribosome system Ribo-T supports cell proliferation though at a reduced rate. Here the authors show this is due to slower ribosome assembly instead of reduced functionality.

    • Nikolay A. Aleksashin
    • , Margus Leppik
    •  & Alexander S. Mankin
  • Article
    | Open Access

    The peptide hormone GLP-1 has the potential to be a remedy for diabetes type II, yet is unstable. Here, the authors synthesized α-peptide-oligourea hybrid analogues of GLP-1 some of which showing significantly prolonged activity in vivo.

    • Juliette Fremaux
    • , Claire Venin
    •  & Sébastien R. Goudreau
  • Article
    | Open Access

    Two-photon absorption capacity of azobenzene photoswitches usually comes with a reduction in thermal stability. Here, the authors developed photoswitches with high two-photon sensitivity and enhanced cis isomer thermal lifetime for the control of glutamate receptors.

    • Gisela Cabré
    • , Aida Garrido-Charles
    •  & Ramon Alibés
  • Article
    | Open Access

    There are only few MRI-compatible calcium reporters and they are limited to measuring extracellular calcium levels. Here the authors develop and validate a cell-permeable, manganese-based paramagnetic MRI contrast agent that enables monitoring intracellular calcium signals in vivo in the rat brain.

    • Ali Barandov
    • , Benjamin B. Bartelle
    •  & Alan Jasanoff
  • Article
    | Open Access

    The enzyme serine hydroxymethyltransferase (SHMT) has been implicated in several diseases, however is hard to investigate. Here, the authors used a design strategy based on the retro-aldol-type reaction catalyzed by SHMT to develop SHMT-responsive fluorescence and 19F NMR molecular probes.

    • Hiroshi Nonaka
    • , Yuki Nakanishi
    •  & Shinsuke Sando
  • Article
    | Open Access

    Premature termination codon suppression therapy could be used to treat a range of genetic disorders. Here the authors present a high-throughput cell-based assay to identify anticodon engineered tRNAs with high suppression activity.

    • John D. Lueck
    • , Jae Seok Yoon
    •  & Christopher A. Ahern
  • Article
    | Open Access

    Analogue regulation of gene expression is important for normal function in mammals but existing genetic technologies are designed to achieve ON/OFF control. Here the authors develop synthetic microRNA silencing-mediated fine-tuners (miSFITs) to precisely control target gene expression levels.

    • Yale S. Michaels
    • , Mike B. Barnkob
    •  & Tudor A. Fulga
  • Article
    | Open Access

    Mother Nature is a valuable resource for the discovery of drug and agricultural chemicals. Here, the authors show that 7-deoxy-sedoheptulose produced by a cyanobacterium is an antimicrobial and herbicidal compound that acts through inhibition of 3-dehydroquniate synthase in the shikimate pathway.

    • Klaus Brilisauer
    • , Johanna Rapp
    •  & Karl Forchhammer
  • Article
    | Open Access

    Membraneless compartments have been theorized to be prebiotic micro-compartments as they spontaneously encapsulate RNA and proteins. Here, the authors report membraneless compartments can enhance RNA chemistries, affecting template directed RNA polymerization and stimulating nucleic acid enzymes.

    • Raghav R. Poudyal
    • , Rebecca M. Guth-Metzler
    •  & Philip C. Bevilacqua
  • Article
    | Open Access

    Bacterial cellulose (BC) is a ubiquitous biomaterial, but functionalization relies on modification processes which have low reaction efficiency and can cause pollution. Here the authors develop an environmental friendly in-situ fermentation method using fluorescein labelled glucose to produce fluorescent BC.

    • Minghong Gao
    • , Juan Li
    •  & Haibo Zhang
  • Article
    | Open Access

    Little is known about the degradation pathway of cyclic imines that are frequently found in bioactive secondary metabolites. Here, the authors found and characterised a copper amine oxidase, HarA that catalyses a ring-opening reaction of cyclic imine in harmaline and oxidative deamination of amines.

    • Toshiki Nagakubo
    • , Takuto Kumano
    •  & Michihiko Kobayashi
  • Article
    | Open Access

    The origin of phospholipids, the primary constituents of cell membranes, is uncertain. Here, the authors develop an in vitro system to synthesize phospholipid molecules from water-soluble single-chain amphiphilic precursors via a reaction catalysed by the mycobacterial ligase FadD10.

    • Ahanjit Bhattacharya
    • , Roberto J. Brea
    •  & Neal K. Devaraj
  • Article
    | Open Access

    Transient oligomeric species of the amyloid-β peptide (Aβ42) have been identified as key pathogenic agents in Alzheimer’s disease. Here the authors find that the aminosterol trodusquemine enhances Aβ42 aggregation and suppresses Aβ42-induced toxicity by displacing oligomers from cell membranes.

    • Ryan Limbocker
    • , Sean Chia
    •  & Christopher M. Dobson
  • Article
    | Open Access

    The selective formation of protein bioconjugates under physiological conditions is a challenging task. Here, the authors report that 1,4-dinitroimidazoles are reagents of choice for protein bioconjugation at either cysteine or lysine sites within short times and provide facile access to peptide macrocycles.

    • Qunfeng Luo
    • , Youqi Tao
    •  & Huan Wang
  • Article
    | Open Access

    PROTACs enable targeted protein degradation by recruiting an E3 ligase to a specific substrate but the determinants of selectivity are not fully understood. Here, the authors show that varying the linker between warhead and E3 ligand and the orientation of the E3 ligase allow tuning PROTAC selectivity toward different p38 isoforms.

    • Blake E. Smith
    • , Stephen L. Wang
    •  & Craig M. Crews
  • Article
    | Open Access

    Spontaneous activity shifts at constant experimental conditions are widespread among ion channels but the molecular origins are poorly understood. Here, using solid-state NMR and MD simulations, the authors reveal that modal gating shifts in K + channels are caused by large shifts in the channel dynamics which perturb the selectivity filter.

    • Shehrazade Jekhmane
    • , João Medeiros-Silva
    •  & Markus Weingarth
  • Article
    | Open Access

    Squalene epoxidase (SQLE) is a key enzyme in cholesterol biosynthesis and is a target for hypercholesteremia and cancer drug development. Here the authors present the crystal structures of the human SQLE catalytic domain alone and bound with small molecule inhibitors, which will facilitate the development of next-generation SQLE inhibitors.

    • Anil K. Padyana
    • , Stefan Gross
    •  & Gromoslaw A. Smolen
  • Article
    | Open Access

    The demethylase activity of KDM5A is allosterically enhanced by binding of histone H3 to its PHD1 reader domain, through an unknown mechanism. Here the authors show that the PHD1 domain drives ligand-induced allosteric stimulation by stabilizing the binding of substrate to the catalytic domain.

    • James E. Longbotham
    • , Cynthia M. Chio
    •  & Danica Galonić Fujimori
  • Article
    | Open Access

    Cancer cells are metabolically adaptable and the identification of specific vulnerabilities is challenging. Here the authors identify a subset of neuroendocrine cell lines exquisitely sensitive to inhibition of SQLE, an enzyme in the cholesterol biosynthetic pathway, due to the toxic accumulation of pathway intermediate squalene.

    • Christopher E. Mahoney
    • , David Pirman
    •  & Gromoslaw A. Smolen
  • Article
    | Open Access

    The Membrane-Proximal External Region (MPER) of the HIV Env gp41 subunit is a target for broadly neutralizing antibodies. Here, the authors apply super-resolution stimulated emission depletion (STED) microscopy on single virions and provide insights into how the MPER epitope is recognized.

    • Pablo Carravilla
    • , Jakub Chojnacki
    •  & José L. Nieva
  • Article
    | Open Access

    Small molecule metabolites like phenylalanine can form amyloid-like structures but so far this has only been demonstrated in vitro. Here the authors generate a yeast in vivo model of adenine self-assembly and characterize the adenine assemblies in cells by indicative amyloid dye and anti-adenine assemblies antibodies.

    • Dana Laor
    • , Dorin Sade
    •  & Ehud Gazit
  • Article
    | Open Access

    P-glycoprotein, an ATP-binding cassette (ABC) transporter, extrudes a large variety of xenobiotics from the cell which protects tissues from toxins. Here authors solve a pair of X-ray structures of homodimeric P-glycoprotein and resolve structural elements proposed to participate in the mechanism of the transporter.

    • Atsushi Kodan
    • , Tomohiro Yamaguchi
    •  & Hiroaki Kato
  • Article
    | Open Access

    Protein methyltransferases (PMTs) are epigenetic regulatory enzymes with significant therapeutic relevance. Here the authors describe a collection of chemical inhibitors and antagonists to modulate most of the key methylation marks on histones H3 and H4, and use the collection to study of the role of PMTs in mouse and human T cell differentiation.

    • Sebastian Scheer
    • , Suzanne Ackloo
    •  & Cheryl H. Arrowsmith
  • Article
    | Open Access

    Serine synthesis from glucose is required even when serine is available from the environment. Here, the authors explain this paradox by showing that the enzyme PHGDH enables nucleotide synthesis by coordinating anabolic fluxes related to central carbon metabolism, independent of its role in serine production.

    • Michael A. Reid
    • , Annamarie E. Allen
    •  & Jason W. Locasale
  • Article
    | Open Access

    Ring-opening polymerizations of α-amino acid N-carboxyanhydrides to form polypeptides are usually sensitive to moisture, slow and can undergo side reactions. Here the authors use lithium hexamethyldisilazide to initiate α-amino acid N-carboxyanhydride polymerizations that is very fast and can be conducted in an open vessel.

    • Yueming Wu
    • , Danfeng Zhang
    •  & Runhui Liu