Chemical biology articles within Nature Communications

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  • Article
    | Open Access

    Clostridium difficile causes diarrhea and colitis by producing up to three different protein toxins. Here, Tam et al. show that an anthelmintic drug, niclosamide, inhibits the pathogenesis of all three toxins by targeting a host process required for toxin entry into host cells, without disrupting the gut microbiota.

    • John Tam
    • , Therwa Hamza
    •  & Roman A. Melnyk

  • Article
    | Open Access

    The discovery of peptide substrates for enzymes with selective activities is a central goal in chemical biology. Here, the authors develop a hybrid method combining machine learning and experimental testing for fast optimization of peptides for specific, orthogononal functions.

    • Lorillee Tallorin
    • , JiaLei Wang
    •  & Nathan C. Gianneschi

  • Article
    | Open Access

    The software Optimer has aided the programmable one-pot oligosaccharide synthesis with a library of 50 Building BLocks (BBLs). Here, the authors expanded Optimer's validated and virtual libraries of BBLs and developed Auto-CHO, a software which allows the one-pot programmable synthesis of more complex glycans.

    • Cheng-Wei Cheng
    • , Yixuan Zhou
    •  & Chi-Huey Wong

  • Article
    | Open Access

    Day-night cycles in the biochemical composition of phytoplankton remain poorly understood. Here, Becker et al. use lipidomic and transcriptomic data from the North Pacific subtropical gyre to describe a daily cycle of production and consumption of energy-rich lipids by eukaryotic phytoplankton.

    • Kevin W. Becker
    • , James R. Collins
    •  & Benjamin A. S. Van Mooy

  • Article
    | Open Access

    Direct targeting of mutant KRas is challenging and alternative approaches are needed. Here they show glycogen synthase kinase 3 (GSK3) to be required for the growth and survival of human mutant KRas-dependent tumors but dispensable for mutant KRas-independent tumors and show GSK3 inhibition to inhibit in vivo growth of Kras mutant patient-derived pancreatic tumors.

    • Aslamuzzaman Kazi
    • , Shengyan Xiang
    •  & Saïd M. Sebti

  • Article
    | Open Access

    A major goal in neuropharmacology is to develop new tools to effectively test the therapeutic potential of pharmacological agents to treat neurological and psychiatric conditions. Here, authors present an in vivo drug screening system that generates large-scale brain activity maps to be used with machine learning to predict the therapeutic potential of clinically relevant drug leads.

    • Xudong Lin
    • , Xin Duan
    •  & Peng Shi

  • Article
    | Open Access

    Artificial genetic polymers (XNAs) have been explored for their nuclease activity, but XNAzymes have proven challenging to discover by in vitro selection. Here, the authors generate an efficient RNA-cleaving 2’-fluoroarabino nucleic acid enzyme (FANAzyme) by in vitro evolution using natural DNA polymerases.

    • Yajun Wang
    • , Arlene K. Ngor
    •  & John C. Chaput

  • Article
    | Open Access

    The helical transmembrane segments of membrane proteins play central roles in sensory transduction but the mechanistic basis for their function remains unresolved. Here the authors identify regions in the S4 voltage-sensing segment of Shaker potassium channels where local helical structure is reliant upon backbone amide support.

    • Daniel T. Infield
    • , Kimberly Matulef
    •  & Francis I. Valiyaveetil

  • Article
    | Open Access

    Cells communicate through chemical and mechanical signals but emulating these in non-living mimics has been challenging. Here the authors present a porous mimic with a DNA-hydrogel ‘nucleus’ that can communicate through diffusive protein signals.

    • Henrike Niederholtmeyer
    • , Cynthia Chaggan
    •  & Neal K. Devaraj

  • Article
    | Open Access

    Common radical fluorination reagents, such as Selectofluor®, are penalized by the need for metal catalysts and possible oxidation side reactions. Here, the authors reported the synthesis and application of N-fluoro-N-arylsulfonamides (NFASs) as third generation of radical fluorinating reagents to overcome those limitations.

    • Daniel Meyer
    • , Harish Jangra
    •  & Philippe Renaud

  • Article
    | Open Access

    The recognition of the mRNA codon by the tRNA anticodon is crucial for protein synthesis. Here the authors introduce non-standard nucleotides in bacterial and eukaryotic mRNA to reveal the minimal hydrogen bond requirement of codon-anticodon interaction for efficient and accurate translation.

    • Thomas Philipp Hoernes
    • , Klaus Faserl
    •  & Matthias David Erlacher

  • Article
    | Open Access

    Bacillus anthracis causes the infectious disease anthrax. Here, the authors synthesized deoxy glycosides that are effective against B. anthracis and related bacteria and found that these amphiphilic compounds kill bacteria via an unusual mechanism of action.

    • Catarina Dias
    • , João P. Pais
    •  & Amélia P. Rauter

  • Article
    | Open Access

    The construction of complex RNA-delivered genetic circuits in mammalian cells is challenging, though offers advantages over DNA circuits in clinical use. Here the authors construct a set of logic gates that respond to multiple miRNAs and demonstrate an apoptosis-regulatory AND gate.

    • Satoshi Matsuura
    • , Hiroki Ono
    •  & Hirohide Saito

  • Article
    | Open Access

    Diseases such as diabetes and Parkinson's manifest based on interactions between genes and environment. Here, the authors find among a panel of cell types that propargite, a common pesticide, induces pancreatic β-cell and dopamine neuron death and that loss of the gene GSTT1 confers hypersensitivity.

    • Ting Zhou
    • , Tae Wan Kim
    •  & Shuibing Chen

  • Article
    | Open Access

    Polyfluorinated hexopyranoses display unique physical, chemical and biological properties, however their stereoselective synthesis is highly challenging. Here, the authors report a synthetic approach based on the chemical manipulation of inexpensive levoglucosan to obtain heavily fluorinated monosaccharides stereoselectively.

    • Vincent Denavit
    • , Danny Lainé
    •  & Denis Giguère

  • Article
    | Open Access

    In vivo existence of guanine-rich four-stranded RNA structures (G4-RNAs) has been a matter of debate. Here the authors developed a protocol, G4RP-seq, to capture and identify transcriptome-wide G4-RNA, providing insights into the formation of transient G4-RNA in live human cells.

    • Sunny Y. Yang
    • , Pauline Lejault
    •  & David Monchaud

  • Article
    | Open Access

    The precise relationship between neurobehavioural effects and neurotransmitter effects of psychiatric drugs are not always understood. Here the authors develop a database documenting the neurotransmitter response in rats to 258 different neuropsychiatric drugs, and conclude that this neurotransmitter response does not, in general, reflect the current categorisation of those drugs.

    • Hamid R. Noori
    • , Lewis H. Mervin
    •  & Rainer Spanagel

  • Article
    | Open Access

    DNA phosphorothioation (PT-DNA) is a DNA backbone sulfur modification that is recognized by the type-IV restriction endonuclease ScoMcrA. Here the authors provide insights into sulfur recognition by solving the crystal structure of the PT-DNA bound sulfur-binding domain (SBD) from ScoMcrA and they further show that SBD homologs are widely spread among prokaryotes.

    • Guang Liu
    • , Wencheng Fu
    •  & Xinyi He

  • Article
    | Open Access

    Peroxisome proliferator-activated receptor gamma (PPARγ) is a target for insulin sensitizing drugs. Here the authors combine NMR, X-ray crystallography and MD simulations and report a structural mechanism for eliciting PPARγ inverse agonism, where coactivator binding is inhibited and corepressor binding promoted, which causes PPARγ repression.

    • Richard Brust
    • , Jinsai Shang
    •  & Douglas J. Kojetin

  • Article
    | Open Access

    Guaianolides are pharmaceutically interesting molecules. Here, the authors isolate the enzyme kauniolide synthase from feverfew, show that it converts constunolide into a guaianolide via an unusual mechanism of action, and reconstruct the full kauniolide biosynthesis pathway in host organisms.

    • Qing Liu
    • , Arman Beyraghdar Kashkooli
    •  & Harro Bouwmeester

  • Article
    | Open Access

    Giant cell lesions of the jaw (GCLJ) are debilitating benign tumors of unclear origin. The authors identify driver recurrent somatic mutations in TRPV4, KRAS and FGFR1 and show they converge on aberrant activation of the MAPK pathway. Their findings extend the spectrum of TRPV4 channelopathies and provide rationale for targeted therapies at the bedside in GCLJ.

    • Carolina Cavalieri Gomes
    • , Tenzin Gayden
    •  & Nada Jabado

  • Article
    | Open Access

    The activity of several protein kinases is increased upon cellular production of reactive oxygen species, which can cause cysteine oxidation. Here the authors show that sulfenylation of specific cysteine residues within Src induce local structural changes that directly impact its activation.

    • David E. Heppner
    • , Christopher M. Dustin
    •  & Albert van der Vliet

  • Article
    | Open Access

    Activating mutations of the non-receptor protein tyrosine phosphatase SHP2 can cause cancer. Here the authors present the crystal structure of SHP2E76K, the most frequent cancer-associated SHP2 mutation, which adopts an open-state structure and show that the allosteric inhibitor SHP099 can revert SHP2E76K to its closed, autoinhibited conformation.

    • Jonathan R. LaRochelle
    • , Michelle Fodor
    •  & Stephen C. Blacklow

  • Article
    | Open Access

    Myoglobin bound to carbon monoxide undergoes an ultrafast light-induced reaction, which ends up in a photolyzed carbon monoxide and a spin transition of the iron center. Here, the authors employ quantum wavepacket dynamics to show that photolysis precedes the spin transition, a mechanism dominated by strong electron-nuclear couplings.

    • Konstantin Falahati
    • , Hiroyuki Tamura
    •  & Miquel Huix-Rotllant

  • Article
    | Open Access

    The hexahydropyrrolo[2, 3-b]indole (HPI) framework is found in many natural products. Here, the authors discover a P450 enzyme and develop a whole-cell biocatalysis system that produces the HPI naseseazine C (NAS-C) and 30 NAS-C analogs, several of which show neuroprotective properties.

    • Wenya Tian
    • , Chenghai Sun
    •  & Xudong Qu

  • Article
    | Open Access

    Rhabdopeptides are synthesized by non-ribosomal peptide synthetases (NRPSs) and the multiple NRPS subunits interact through docking domains (DD). Here the authors provide insights into DD interaction patterns and present the structures of three N-terminal docking domains (NDD) and a NDD-CDD complex and derive a set of recognition rules for DD interactions.

    • Carolin Hacker
    • , Xiaofeng Cai
    •  & Jens Wöhnert

  • Article
    | Open Access

    Ischemic reperfusion or nutrient deprivation that produces reactive oxygen species can lead to a loss of muscle contractile function. Here the authors show that glutathionylation of the lysine methyltransferase SMYD2 contributes to degradation or disassembly of sarcomeres.

    • Dhanushka N. P. Munkanatta Godage
    • , Garrett C. VanHecke
    •  & Young-Hoon Ahn

  • Article
    | Open Access

    Targeting noncoding nucleic acids with small molecules represents an important and significant challenge in chemical biology and drug discovery. Here the authors characterize DC-34, a small molecule that exhibits selective binding to specific G4 structures, and provide a structural basis for its selectivity

    • David R. Calabrese
    • , Xiang Chen
    •  & John S. Schneekloth Jr.

  • Article
    | Open Access

    Membrane bilayers are made up of a myriad of different lipids that affect membrane proteins, but identifying those specific lipid requirements remains a challenge. Here authors present an engineered thermal-shift screen which reveals specific lipid preferences of eukaryotic and prokaryotic membrane proteins.

    • Emmanuel Nji
    • , Yurie Chatzikyriakidou
    •  & David Drew

  • Article
    | Open Access

    Secondary transporters catalyse substrate translocation across the cell membrane but the role of lipids during the transport cycle remains unclear. Here authors used hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations to understand how lipids regulate the conformational dynamics of secondary transporters.

    • Chloe Martens
    • , Mrinal Shekhar
    •  & Argyris Politis

  • Article
    | Open Access

    Higher order coiled coils with five or more helices can form α-helical barrels. Here the authors show that placing β-branched aliphatic residues along the lumen yields stable and open α-helical barrels, which is of interest for the rational design of functional proteins; whereas, the absence of β-branched side chains leads to unusual low-symmetry α-helical bundles.

    • Guto G. Rhys
    • , Christopher W. Wood
    •  & Derek N. Woolfson

  • Article
    | Open Access

    Diketopiperazine derivatives are bioactive molecules with scaffold formed by the condensation of two amino acids. Here, Yao et al. mine the genomes of Streptomyces strains and identify new biosynthetic machinery for drimentines biosynthesis, which includes cyclodipeptide synthase, prenyltransferase, and terpene cyclase.

    • Tingting Yao
    • , Jing Liu
    •  & Wenli Li

  • Article
    | Open Access

    Designing split protein approaches is time consuming and often results in high background activity due to spontaneous assembly. Here the authors present an automated approach which uses a split energy scoring function to identify optimal protein split sites and reduces spontaneous assembly.

    • Onur Dagliyan
    • , Andrey Krokhotin
    •  & Nikolay V. Dokholyan

  • Article
    | Open Access

    New natural products can be identified via mass spectrometry by excluding all known ones from the analysis, a process called dereplication. Here, the authors extend a previously published dereplication algorithm to different classes of secondary metabolites.

    • Hosein Mohimani
    • , Alexey Gurevich
    •  & Pavel A. Pevzner

  • Article
    | Open Access

    Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a common bioconjugation technique; however oxidative degradation and residual copper may limit its use. Here, the authors show that ppm levels of Cu, generated in situ by solvent-mediated pipe erosion in flow, catalyze the CuAAC reaction with no product degradation.

    • Marine Z. C. Hatit
    • , Linus F. Reichenbach
    •  & Allan J. B. Watson

  • Article
    | Open Access

    Assimilating the abundant one-carbon compounds by an industrially-relevant microorganism can broaden the substrate range and achieve reactions that are difficult for chemical process. Here the authors show a modified serine cycle can convert methanol and CO2 to two-carbon compounds in an engineered E. coli strain.

    • Hong Yu
    •  & James C. Liao

  • Article
    | Open Access

    The bacterial diterpene synthase CotB2 catalyses the cyclisation of geranylgeranyl diphosphate to cyclooctat-9-en7-ol. Here the authors present various CotB2 structures including a trapped abrupt reaction product that were used for molecular dynamic simulations and allowed them to model all intermediates along the reaction cascade.

    • Ronja Driller
    • , Sophie Janke
    •  & Bernhard Loll

  • Article
    | Open Access

    The monoamine oxidase family member LkcE is an enzyme from the lankacidin polyketide biosynthetic pathway, where it catalyzes an amide oxidation followed by an intramolecular Mannich reaction, yielding the polyketide macrocycle. Here the authors characterize LkcE and present several of its crystal structures, which explains the unusual dual activity of LkcE.

    • Jonathan Dorival
    • , Fanny Risser
    •  & Kira J. Weissman

  • Article
    | Open Access

    Strobilurins are fungal metabolites that inspired the creation of β-methoxyacrylate agricultural fungicides. Here, Nofiani et al. identify the strobilurin biosynthesis gene cluster, encoding a polyketide synthase as well as an FAD-dependent oxygenase for an oxidative rearrangement leading to β-methoxyacrylate formation.

    • Risa Nofiani
    • , Kate de Mattos-Shipley
    •  & Russell J. Cox

  • Article
    | Open Access

    Upon ligand binding epidermal growth factor receptor (EGFR) dimerizes and activates its intrinsic kinase to auto-phosphorylate EGFR. Here, the authors engineer and image a FRET-based conformational EGFR indicator which reveals that activation loop phosphorylation induces a catalytically active conformation in EGFR monomers.

    • Martin Baumdick
    • , Márton Gelléri
    •  & Philippe I. H. Bastiaens

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