Chemical biology articles within Nature Communications

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  • Article
    | Open Access

    SMNDC1 is a splicing factor that binds arginine methylation with its Tudor domain. Here, the authors study the protein’s phase-separating behavior and develop small-molecule Tudor domain inhibitors that perturb SMNDC1 function.

    • Lennart Enders
    • , Marton Siklos
    •  & Stefan Kubicek

  • Article
    | Open Access

    Branched chain ketoacid dehydrogenase kinase (BDK) inhibits the activity of branched chain ketoacid dehydrogenase and branched chain amino acid degradation, implicated in several diseases. Here, the authors discover a BDK inhibitor and degrader that shows efficacy in rodent metabolism and heart failure models, as well as another class of BDK inhibitors that stabilizes BDK.

    • Rachel J. Roth Flach
    • , Eliza Bollinger
    •  & Kevin J. Filipski

  • Article
    | Open Access

    Here the authors use fast kinetics, X-ray crystallography, and cryo-EM to uncover the mechanism of ribosome inhibition by amikacin and kanamycin. They find that amikacin binds near the P-site tRNA, offering new strategies to fight antibiotic resistance.

    • Savannah M. Seely
    • , Narayan P. Parajuli
    •  & Matthieu G. Gagnon

  • Article
    | Open Access

    Replacement of oxoamide units with thioamides in peptide therapeutics is a valuable tactic to improve biological activity and resistance to enzymatic hydrolysis. Here, the authors develop a direct coupling of readily available nitroalkane and amines with elemental sulfur and base and provide an efficient way to form thioamides and thiopeptides.

    • Xiaonan Wang
    • , Silong Xu
    •  & Jing Li

  • Article
    | Open Access

    Agonists of the cytosolic DNA-sensing STING pathway potently remodel the tumour immune microenvironment to support anti-tumour adaptive immunity, but at the expense of adverse systemic inflammation. Here authors exchange the STING agonist MSA-2 with its prodrugs that are suitable for nano-liposomal delivery and thus achieve increased efficiency and decreased toxicity.

    • Xiaona Chen
    • , Fanchao Meng
    •  & Hangxiang Wang

  • Article
    | Open Access

    Here, authors introduced negative charges in the transmembrane helices in Kir2.2 channels generating pH-dependent sub-conductances. Molecular dynamics simulations show how protonation results in step-wise alterations of ion pooling and hence conductance, appearing as gated substates.

    • Grigory Maksaev
    • , Michael Bründl-Jirout
    •  & Colin G. Nichols

  • Article
    | Open Access

    (1,3;1,4)-β-d-Glucans are widely distributed in many organisms, but little is known about the enzymes responsible for their synthesis outside the grasses. Here, the authors report on the presence of (1,3;1,4)-β-d-glucans in the exopolysaccharides of the Gram-positive bacterium Romboutsia ilealis and identify and characterize the (1,3;1,4)-β-d-glucan synthase RiGT2.

    • Shu-Chieh Chang
    • , Mu-Rong Kao
    •  & Yves S. Y. Hsieh

  • Article
    | Open Access

    Here, the authors demonstrate that inhibition of PTP1B and PTPN2 in tumor cells and T-cells with a small molecule inhibitor represses the growth of immunogenic and cold tumors, and enhances response to anti-PD-1 immunotherapy without promoting immune-related toxicities.

    • Shuwei Liang
    • , Eric Tran
    •  & Tony Tiganis

  • Article
    | Open Access

    The lack of a universal platform for PROTAC development remains a major bottleneck. Here, the authors report modular DNA framework-based PROTACs (DbTACs) that enable precise control of the linker length and selective degradation of diverse targets in different cellular compartments using various warheads.

    • Li Zhou
    • , Bin Yu
    •  & Yi Ma

  • Article
    | Open Access

    The physiological roles of supersulphides and the enzymes that trigger their production in various airway diseases are not fully understood. Here, the authors show in animal models of viral and chronic lung diseases that supersulphide production can mitigate lung pathology and lethal effects, highlighting their protective role and potential as a therapeutic target.

    • Tetsuro Matsunaga
    • , Hirohito Sano
    •  & Takaaki Akaike

  • Article
    | Open Access

    Maize has an unconventional proanthocyanidin (PA) biosynthetic pathway which produces rare stereoisomers of PA monomers and dimers, highlighting an opportunity for further improving the nutritional value of maize.

    • Nan Lu
    • , Ji Hyung Jun
    •  & Richard A. Dixon

  • Article
    | Open Access

    The binding of small molecules to the double stranded DNA may significantly alter its stability and functionality, which is the basis for many therapeutic and sensing applications. Here, the authors report that DNA binders can be used to program reaction pathways of a dynamic DNA reaction, where DNA strand displacement can be tuned quantitatively according to the affinity, charge, and concentrations of a given DNA binder.

    • Junpeng Xu
    • , Guan Alex Wang
    •  & Feng Li

  • Article
    | Open Access

    Nuclear receptors (NR) are drug-responsive master regulators. Here, authors map DNA binding profiles of all human NRs. Their MinSeq Find algorithm identifies masked NR binding sites in genomes and maps ~10% of orphan SNPs linked to numerous diseases.

    • Devesh Bhimsaria
    • , José A. Rodríguez-Martínez
    •  & Aseem Z. Ansari

  • Article
    | Open Access

    The structural basis of integrin signaling in health and disease is not fully understood. Here, the authors determine the cryoEM structure of full-length platelet integrin αIIbβ3 in its apo and eptifibatide-bound conformations in a native membrane environment.

    • Brian D. Adair
    • , Jian-Ping Xiong
    •  & M. Amin Arnaout

  • Article
    | Open Access

    EPAC1 is a cAMP-activated guanine nucleotide exchange factor (GEF) for Rap GTPases and a major transducer of cAMP signaling. Here, the authors show anionic membranes can activate EPAC1 independently of cAMP, increase its affinity for cAMP by two orders of magnitude, and synergize with cAMP to yield maximal GEF activity.

    • Candice Sartre
    • , François Peurois
    •  & Jacqueline Cherfils

  • Article
    | Open Access

    Homogeneous engineering of proteins is promising to study biological functions and for the development of therapeutic conjugates. Here, the authors report a one-pot multicomponent Furan-Thiol-Amine reaction for diverse applications, including labelling of peptides, synthesis of macrocyclic and stapled peptides, selective modification of different proteins with varying payloads, and labelling of lysine and cysteine in a complex human proteome.

    • Yuwen Wang
    • , Patrick Czabala
    •  & Monika Raj

  • Article
    | Open Access

    The mechanism of action of the antibacterial tripeptide AMC-109 is unclear. Here, Melcrová et al. show that AMC-109 self-assembles into stable aggregates with a cationic surface, and then individual peptides insert into the bacterial membrane and disrupt membrane nanodomains, thus affecting membrane function without forming pores.

    • Adéla Melcrová
    • , Sourav Maity
    •  & Wouter H. Roos

  • Article
    | Open Access

    Diterpene synthase VenA catalyses the synthesis of venezuelaene A with a unique 5-5-6-7 tetracyclic skeleton from geranylgeranyl pyrophosphate. Here, the authors report crystal structures of apo- and holo-VenA, provide mechanistic insights into its substrate selectivity and promiscuity, and engineer VenA into a sesterterpene synthase.

    • Zhong Li
    • , Lilan Zhang
    •  & Shengying Li

  • Article
    | Open Access

    Current clinical methods for assessing kidney function report an aggregate value for both kidneys, and lack the ability to say which kidney is dysfunctioning or even to localize the dysfunction to a region of renal pathology. Here, the authors show that an injectable dye can be used to map kidney function by magnetic resonance imaging, offering a safer alternative than existing dyes for the spatial evaluation of kidney health.

    • Nicholas D. Calvert
    • , Alexia Kirby
    •  & Adam J. Shuhendler

  • Article
    | Open Access

    Fatty acids are fundamental biomolecular building blocks that are characterized by extraordinary structural diversity and present a formidable analytical challenge. Here the authors introduce a discovery workflow for de novo identification that adds more than 100 fatty acids to the human lipidome.

    • Jan Philipp Menzel
    • , Reuben S. E. Young
    •  & Stephen J. Blanksby

  • Article
    | Open Access

    Live-cell RNA imaging with high spatial and temporal resolution remains a major challenge. Here the authors design spirocyclic rhodamine probes that enable a fluorescent light-up aptamer system suitable for visualizing RNAs in live or fixed cells with two different super-resolution microscopy modalities SMLM and STED.

    • Daniel Englert
    • , Eva-Maria Burger
    •  & Murat Sunbul

  • Article
    | Open Access

    Endonucleases play crucial roles in various biological processes but endonucleases that target small non-coding RNAs have not been reported. Here, the authors combined the metal binding non-canonical amino acid BpyAla and a high affinity binder to engineer a catalyst that degrades small non-coding RNAs.

    • Noreen Ahmed
    • , Nadine Ahmed
    •  & John Paul Pezacki

  • Article
    | Open Access

    Epichaperomics allow the study of protein-protein interactions and their alterations, but probes have been limited to capturing HSP90 epichaperomes. Here, the authors introduce and validate a toolset of HSP70 epichaperome ligands, and use them in epichaperomics to identify a mechanism with which cancer cells can enhance the fitness of mitotic protein networks.

    • Anna Rodina
    • , Chao Xu
    •  & Gabriela Chiosis

  • Article
    | Open Access

    The fungal dioxygenase AsqJ catalyses the conversion of benzo[1,4]diazepine-2,5-diones into quinolone antibiotics, and can also catalyse the production of quinazolinones. Here, the authors perform comprehensive substrate promiscuity mapping of AsqJ revealing its large tolerance towards various substrates, giving biocatalytic access to a plethora of biomedically valuable heterocyclic frameworks.

    • Manuel Einsiedler
    •  & Tobias A. M. Gulder

  • Article
    | Open Access

    In this work, the authors synthetized hydrogels that mimic cryptic sites in the native extracellular matrix (ECM) using switch peptides. They report how in response to enzymes on the surface of endothelial cells the inert matrix is transformed into a bioadhesive synthetic ECM.

    • Yumeng Zhu
    • , Yulia Shmidov
    •  & John B. Matson

  • Article
    | Open Access

    Cannabidiol (CBD), the nonpsychoactive component in cannabis, is an effective treatment for epilepsy and pain. Here, authors explored the mode of action of CBD on hNav1.7 channels through two distinct binding sites, suggesting a direct stabilization of the inactivated state of channels.

    • Jian Huang
    • , Xiao Fan
    •  & Nieng Yan

  • Article
    | Open Access

    Lipoic acid is a food supplement and approved neuropathy drug but lacks known molecular targets. Here, Lechner et al. employ chemoproteomic target deconvolution to demonstrate that (R)- but not (S)-lipoic acid stereoselectively inhibits histone deacetylases at physiologically achievable doses.

    • Severin Lechner
    • , Raphael R. Steimbach
    •  & Bernhard Kuster

  • Article
    | Open Access

    Natural proteins exhibit rich structural diversity based on the folds of an invariably linear chain. Here the authors design a single-domain GFP catenane as the counterpart of conventional linear GFP with enhanced thermal resilience and to provide a robust scaffold for making fusion protein catenanes.

    • Zhiyu Qu
    • , Jing Fang
    •  & Wen-Bin Zhang

  • Article
    | Open Access

    Compact RNA structural motifs control many aspects of gene expression, but methods for their identification are lacking. Here the authors present a sequencing-based terbium probing approach to detect complex 3D structural elements, which can be used to pinpoint potential riboregulatory elements.

    • Shivali Patel
    • , Alec N. Sexton
    •  & Anna Marie Pyle

  • Article
    | Open Access

    Incorporating bioorthogonally-modified amino acids into newly synthesized proteins allows studying the nascent proteome, but current methods often require special conditions or are toxic to cells. Here, the authors develop a method that uses β-ethynylserine to label nascent proteins under standard conditions without harming cells.

    • Bob J. Ignacio
    • , Jelmer Dijkstra
    •  & Kimberly M. Bonger

  • Article
    | Open Access

    SARS-CoV-2 genome turnover is mediated by its N protein, but precise parameters driving the necessary RNA specificity have remained enigmatic. Here, Korn et al. reveal N’s N-terminal domain to distinguish regulatory viral RNA motifs with a preference for transiently folded elements of functional impact.

    • Sophie Marianne Korn
    • , Karthikeyan Dhamotharan
    •  & Andreas Schlundt

  • Article
    | Open Access

    NADP(H) is a crucial cofactor, acting as a reducing agent in numerous pathways in living organisms. Here the authors report a ratiometric biosensor named NERNST, which can be used to estimate the NADP(H) redox status in bacterial, plant and animal cells and organelles.

    • Pamela E. Molinari
    • , Adriana R. Krapp
    •  & Matias D. Zurbriggen

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