An aminoacylation ribozyme evolved from a natural tRNA-sensing T-box riboswitch

Posted on Mar 23rd, 2020 - By Satoshi Ishida

Nature Chemical Biology, Published online: 23 March 2020; doi:10.1038/s41589-020-0500-6The authors develop a ribozyme, Tx2.1, that is capable of aminoacylating tRNA with specificity for the anticodon from directed evolution of a T-box riboswitch. Tx2.1 could be used to charge non-natural amino acids in an in vitro translation…

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The origin of genomic <i>N</i><sup>6</sup>-methyl-deoxyadenosine in mammalian cells

Posted on Mar 23rd, 2020 - By Michael U. Musheev

Nature Chemical Biology, Published online: 23 March 2020; doi:10.1038/s41589-020-0504-2A metabolic labeling method reveals that genomic N6-methyl-deoxyadenosine in mammalian cell lines originates not from direct methylation in DNA, but from a misincorporation of the metabolite of…

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A tell-tale absence

Posted on Mar 20th, 2020 - By Caitlin Deane

Nature Chemical Biology, Published online: 20 March 2020; doi:10.1038/s41589-020-0513-1A tell-tale…

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Tick tock

Posted on Mar 20th, 2020 - By Yiyun Song

Nature Chemical Biology, Published online: 20 March 2020; doi:10.1038/s41589-020-0515-zTick…

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Unifying principles of bifunctional, proximity-inducing small molecules

Posted on Mar 20th, 2020 - By Christopher J. Gerry

Nature Chemical Biology, Published online: 20 March 2020; doi:10.1038/s41589-020-0469-1This Perspective describes the chemical and biophysical principles common to all bifunctional, proximity-inducing small molecules. It also discusses the underappreciated diversity of their chemical structures and biological…

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Locked on target

Posted on Mar 20th, 2020 - By Caitlin Deane

Nature Chemical Biology, Published online: 20 March 2020; doi:10.1038/s41589-020-0512-2Locked on…

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A gut reaction

Posted on Mar 20th, 2020 - By Mirella Bucci

Nature Chemical Biology, Published online: 20 March 2020; doi:10.1038/s41589-020-0514-0A gut…

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<span class=”small-caps”>d</span>-Cycloserine destruction by alanine racemase and the limit of irreversible inhibition

Posted on Mar 16th, 2020 - By Cesira de Chiara

Nature Chemical Biology, Published online: 16 March 2020; doi:10.1038/s41589-020-0498-9d-Cycloserine inactivates alanine racemase by forming an adduct with the pyridoxal 5′-phosphate cofactor, but structural and spectroscopic analyses reveal that reactivation occurs on adduct hydrolysis and product rearrangement to a stable…

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Atomic structure of potato virus X, the prototype of the <i>Alphaflexiviridae</i> family

Posted on Mar 16th, 2020 - By Alessandro Grinzato

Nature Chemical Biology, Published online: 16 March 2020; doi:10.1038/s41589-020-0502-4A cryo-EM structure of potato virus X shows that virions are formed by repeats of segments of coat protein protomers arranged in a left-handed helical structure and reveals details of the RNA–capsid interactions, which shed light on virus…

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A new path to tyrosine sulfation

Posted on Mar 16th, 2020 - By Chang C. Liu

Nature Chemical Biology, Published online: 16 March 2020; doi:10.1038/s41589-020-0482-4Tyrosine sulfation is a common post-translational modification known to play critical roles in multiple bioprocesses. A cleverly engineered mammalian expanded genetic code now enables the direct co-translational incorporation of tyrosine sulfates into proteins to study their function in cellular…

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Activation of the α<sub>2B</sub> adrenoceptor by the sedative sympatholytic dexmedetomidine

Posted on Mar 9th, 2020 - By Daopeng Yuan

Nature Chemical Biology, Published online: 09 March 2020; doi:10.1038/s41589-020-0492-2A cryo-EM structure of the GPCR α2B adrenergic receptor (α2BAR) in complex with the selective agonist dexmedetomidine and the G protein Go suggests a mechanism of selective activation and provides insights into G-protein coupling…

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A bifunctional O-antigen polymerase structure reveals a new glycosyltransferase family

Posted on Mar 9th, 2020 - By Bradley R. Clarke

Nature Chemical Biology, Published online: 09 March 2020; doi:10.1038/s41589-020-0494-0Structural characterization of WbbM, an enzyme involved in O2a-antigen biosynthesis in Klebsiella pneumoniae, reveals two unique active sites with galactopyranosyl- or galactofuranosyl-transferase activities for oligosaccharide…

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A DNA-based fluorescent probe maps NOS3 activity with subcellular spatial resolution

Posted on Mar 9th, 2020 - By Maulik S. Jani

Nature Chemical Biology, Published online: 09 March 2020; doi:10.1038/s41589-020-0491-3A pair of fluorescent DNA-based probes for nitric oxide reveals that nitric oxide synthase 3 activity in the trans-Golgi network is essential for Golgi structural integrity, despite being tenfold less active there than at the plasma…

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Paradoxical mitotic exit induced by a small molecule inhibitor of APC/C<sup>Cdc20</sup>

Posted on Mar 9th, 2020 - By Katherine V. Richeson

Nature Chemical Biology, Published online: 09 March 2020; doi:10.1038/s41589-020-0495-zA small-molecule ligand of the APC/C activator Cdc20, which prolongs mitosis in unperturbed cells, instead shortens mitosis when the spindle checkpoint is activated, producing an opposite effect in a different regulatory…

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Hitchhiking into the cell

Posted on Mar 9th, 2020 - By Douglas B. Kell

Nature Chemical Biology, Published online: 09 March 2020; doi:10.1038/s41589-020-0489-xThe mechanisms by which bioactive drugs get into their target cells is a question that has been greatly neglected. A new survey with CRISPR–Cas9 shows the widespread importance of protein transporters called solute carriers…

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A widespread role for SLC transmembrane transporters in resistance to cytotoxic drugs

Posted on Mar 9th, 2020 - By Enrico Girardi

Nature Chemical Biology, Published online: 09 March 2020; doi:10.1038/s41589-020-0483-3A set of CRISPR–Cas9-based genetic screens in a haploid human cell line identifies more than 200 gene–drug associations involving solute carriers (SLCs), transporters important for the uptake and activity of cytotoxic…

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Deep mutational scanning reveals the structural basis for α-synuclein activity

Posted on Mar 9th, 2020 - By Robert W. Newberry

Nature Chemical Biology, Published online: 09 March 2020; doi:10.1038/s41589-020-0480-6Deep mutational scanning reveals that α-synuclein adopts a membrane-bound α-helix conformation with increasing dynamics towards the C terminus. This helical conformation is associated with its…

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A gene signal amplifier platform for monitoring the unfolded protein response

Posted on Mar 9th, 2020 - By Carlos A. Origel Marmolejo

Nature Chemical Biology, Published online: 09 March 2020; doi:10.1038/s41589-020-0497-xEngineering of a synthetic circuit that couples transcriptional and protein turnover regulation to a fluorescent protein readout enables sensitive monitoring and amplification of gene expression signals from the unfolded protein response…

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A drug discovery platform to identify compounds that inhibit EGFR triple mutants

Posted on Feb 24th, 2020 - By Punit Saraon

Nature Chemical Biology, Published online: 24 February 2020; doi:10.1038/s41589-020-0484-2A high-throughput small-molecule drug screening platform enabled the detection of compounds targeting the functional interactions of receptor tyrosine kinases and identifies four new EGFR triple-mutant…

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Endosome motility defects revealed at super-resolution in live cells using HIDE probes

Posted on Feb 24th, 2020 - By Aarushi Gupta

Nature Chemical Biology, Published online: 24 February 2020; doi:10.1038/s41589-020-0479-zHIDE probes were developed for long time-lapse imaging of endolysosomes and their dynamics at super-resolution. These probes enabled analyses of endosome motility in primary fibroblasts from patients with Niemann–Pick C with distinct mutations in…

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Restoring the balance

Posted on Feb 20th, 2020 - By Caitlin Deane

Nature Chemical Biology, Published online: 20 February 2020; doi:10.1038/s41589-020-0485-1Restoring the…

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Investigating PIs

Posted on Feb 20th, 2020 - By Mirella Bucci

Nature Chemical Biology, Published online: 20 February 2020; doi:10.1038/s41589-020-0487-zInvestigating…

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Biased M1-muscarinic-receptor-mutant mice inform the design of next-generation drugs

Posted on Feb 20th, 2020 - By Sophie J. Bradley

Nature Chemical Biology, Published online: 20 February 2020; doi:10.1038/s41589-019-0453-9Use of receptor variants in knock-in mice to dissect phosphorylation-dependent signaling from G protein-dependent signaling mediated by acetylcholine receptor M1 mAChR defines the ability of receptor ligands to modulate anxiety and locomotion…

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Leveraging bias to your advantage

Posted on Feb 20th, 2020 - By Sean P. Moran

Nature Chemical Biology, Published online: 20 February 2020; doi:10.1038/s41589-020-0468-2Characterization of biased receptor signaling has ushered in opportunities for unprecedented control of G-protein-coupled receptors. Elucidation of distinct M1 muscarinic acetylcholine receptor signaling pathways and development of biased ligands may offer novel and safer Alzheimer’s disease…

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Cryo-electron microscopy for the study of virus assembly

Posted on Feb 20th, 2020 - By Daniel Luque

Nature Chemical Biology, Published online: 20 February 2020; doi:10.1038/s41589-020-0477-1Cryo-EM and Cryo-ET have emerged as useful tools to study the efficient and dynamic processes of the viral…

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Hooked on vitamins

Posted on Feb 20th, 2020 - By Grant Miura

Nature Chemical Biology, Published online: 20 February 2020; doi:10.1038/s41589-020-0486-0Hooked on…

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A stop to signaling

Posted on Feb 20th, 2020 - By Yiyun Song

Nature Chemical Biology, Published online: 20 February 2020; doi:10.1038/s41589-020-0488-yA stop to…

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Rendezvous of Retro-2 at the ER

Posted on Feb 17th, 2020 - By Hesso Farhan

Nature Chemical Biology, Published online: 17 February 2020; doi:10.1038/s41589-020-0475-3Retro-2 is a drug that protects cells against bacterial and plant toxins by arresting their trafficking in endosomes. New data show that the target for Retro-2 is surprisingly not within the endosomal system, but on the endoplasmic…

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Keth-seq for transcriptome-wide RNA structure mapping

Posted on Feb 3rd, 2020 - By Xiaocheng Weng

Nature Chemical Biology, Published online: 03 February 2020; doi:10.1038/s41589-019-0459-3The authors designed a chemical probe, azido-kethoxal, to specifically label guanosine in single-strand RNAs in live cells that could be used to determine transcriptome-wide RNA secondary…

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A dual function PUS enzyme

Posted on Jan 23rd, 2020 - By Wen Zhang

Nature Chemical Biology, Published online: 23 January 2020; doi:10.1038/s41589-019-0450-zThe traditional function of pseudouridine synthases is to convert uridine residues in RNA to pseudouridines. A study reveals a new function for the human PUS10 protein, which enhances micro-RNA maturation in addition to tRNA…

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New beginnings

Posted on Jan 23rd, 2020 - By Yiyun Song

Nature Chemical Biology, Published online: 23 January 2020; doi:10.1038/s41589-020-0466-4New…

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Spying on the microbiome

Posted on Jan 23rd, 2020 - By Caitlin Deane

Nature Chemical Biology, Published online: 23 January 2020; doi:10.1038/s41589-020-0463-7Spying on the…

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Chris Dobson (1949–2019)

Posted on Jan 23rd, 2020 - By Tuomas P. J. Knowles

Nature Chemical Biology, Published online: 23 January 2020; doi:10.1038/s41589-019-0456-6Chris Dobson passed away on September 8th, leaving a wide-reaching legacy. He is best known for revealing the generality of the phenomenon of protein misfolding and aggregation and has provided inspiration for generations of…

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Stress-tolerant non-conventional microbes enable next-generation chemical biosynthesis

Posted on Jan 23rd, 2020 - By Sarah Thorwall

Nature Chemical Biology, Published online: 23 January 2020; doi:10.1038/s41589-019-0452-xThe native stress-tolerant phenotypes of various non-conventional microbes have the potential to enable more efficient bioprocessing for chemical production, addressing certain design challenges encountered when using model production…

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Spores hit the spot

Posted on Jan 23rd, 2020 - By Chao Zhong

Nature Chemical Biology, Published online: 23 January 2020; doi:10.1038/s41589-019-0451-yEngineered living materials (ELMs) with the qualities of both programmable functionalities and environmental tolerance are rare. 3D printing of bacterial spores into resilient living materials provides a viable route to fabricate ELMs that integrate these material…

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Lipid hijacking

Posted on Jan 23rd, 2020 - By Mirella Bucci

Nature Chemical Biology, Published online: 23 January 2020; doi:10.1038/s41589-020-0465-5Lipid…

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Noise reduction

Posted on Jan 23rd, 2020 - By Grant Miura

Nature Chemical Biology, Published online: 23 January 2020; doi:10.1038/s41589-020-0464-6Noise…

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Molecular basis for receptor tyrosine kinase A-loop tyrosine transphosphorylation

Posted on Jan 20th, 2020 - By Lingfeng Chen

Nature Chemical Biology, Published online: 20 January 2020; doi:10.1038/s41589-019-0455-7X-ray crystallography, solution NMR and biochemical and cell-based analyses reveal a model where catalytically repressed receptor tyrosine kinases accomplish activation loop (A-loop) tyrosine…

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Structural equilibrium underlying ligand-dependent activation of β<sub>2</sub>-adrenoreceptor

Posted on Jan 20th, 2020 - By Shunsuke Imai

Nature Chemical Biology, Published online: 20 January 2020; doi:10.1038/s41589-019-0457-5NMR structural analysis of an active state of the β2-adrenergic receptor defines a unique orientation for the intracellular half of TM6, responsible for G-protein binding, including an equilibrium among three conformations of a key…

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Biased modulators of NMDA receptors control channel opening and ion selectivity

Posted on Jan 20th, 2020 - By Riley E. Perszyk

Nature Chemical Biology, Published online: 20 January 2020; doi:10.1038/s41589-019-0449-5A series of positive allosteric modulators of NMDA receptors that can increase agonist potency, increase channel-open probability, and slow receptor deactivation can also decrease single-channel conductance and decrease calcium…

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Author Correction: Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex

Posted on Jan 15th, 2020 - By Dirksen E. Bussiere

Nature Chemical Biology, Published online: 15 January 2020; doi:10.1038/s41589-020-0471-7Author Correction: Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase…

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Publisher Correction: An efficient gene knock-in strategy using 5′-modified double-stranded DNA donors with short homology arms

Posted on Jan 15th, 2020 - By Yi Yu

Nature Chemical Biology, Published online: 15 January 2020; doi:10.1038/s41589-020-0470-8Publisher Correction: An efficient gene knock-in strategy using 5′-modified double-stranded DNA donors with short homology…

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A fungal family of lytic polysaccharide monooxygenase-like copper proteins

Posted on Jan 13th, 2020 - By Aurore Labourel

Nature Chemical Biology, Published online: 13 January 2020; doi:10.1038/s41589-019-0438-8The X325 protein family is highly similar to lytic polysaccharide monooxygenases (LPMOs) in regulation, structure and copper coordination by a histidine brace, yet lacks LPMO activity and suggests the evolution of an alternative function in…

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Rewiring E2 enzymes

Posted on Jan 13th, 2020 - By Koichi Sato

Nature Chemical Biology, Published online: 13 January 2020; doi:10.1038/s41589-019-0454-8The site-specific monoubiquitination of FANCD2 is crucial for the Fanconi anemia DNA repair pathway and tumor suppression. This modification is mediated by the E2 enzyme UBE2T and the E3 ligase FANCL through a novel allosteric…

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Lipid droplets can promote drug accumulation and activation

Posted on Jan 13th, 2020 - By Ramin Dubey

Nature Chemical Biology, Published online: 13 January 2020; doi:10.1038/s41589-019-0447-7Lasonolide A is hydrolyzed into a cytotoxic metabolite by a lipid droplet-associated orphan serine hydrolase, showing that lipid droplets can promote drug toxicity by both accumulating and metabolizing drugs in…

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A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis

Posted on Jan 13th, 2020 - By Sarela Garcia-Santamarina

Nature Chemical Biology, Published online: 13 January 2020; doi:10.1038/s41589-019-0437-9In the fungal pathogen Cryptococcus neoformans, Bim1 is a copper-binding lytic polysaccharide monooxygenase-like protein that participates in copper uptake in concert with the Ctr1 importer to drive virulence mechanisms during fungal…

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Molecular basis for fibroblast growth factor 23 <i>O</i>-glycosylation by GalNAc-T3

Posted on Jan 13th, 2020 - By Matilde de las Rivas

Nature Chemical Biology, Published online: 13 January 2020; doi:10.1038/s41589-019-0444-xPolypeptide GalNAc-transferase T3 catalyzes the specific glycosylation of threonine-178 of fibroblast growth factor 23, and structural insights reveal a unique lectin-based mechanism of substrate…

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Reprogramming fatty acyl specificity of lipid kinases via C1 domain engineering

Posted on Jan 13th, 2020 - By Timothy B. Ware

Nature Chemical Biology, Published online: 13 January 2020; doi:10.1038/s41589-019-0445-9A chemoproteomics and protein engineering strategy to investigate metabolic activity of lipid kinases led to assignment of a key role for atypical C1 domains in directing fatty acyl specificity of diacylglycerol kinase function in live…

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Chain alignment of collagen I deciphered using computationally designed heterotrimers

Posted on Jan 6th, 2020 - By Abhishek A. Jalan

Nature Chemical Biology, Published online: 06 January 2020; doi:10.1038/s41589-019-0435-yDesigned heterotrimers of collagen I, locked in three possible chain registers, enable structural and functional characterization of each permutation, leading to identification of the AAB heterotrimer as the most active and therefore likely to occur…

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A tunable orthogonal coiled-coil interaction toolbox for engineering mammalian cells

Posted on Jan 6th, 2020 - By Tina Lebar

Nature Chemical Biology, Published online: 06 January 2020; doi:10.1038/s41589-019-0443-yA set of orthogonal coiled-coil peptide heterodimers were developed to enable control of protein localization as well as transcriptional regulation by enhancing effector recruitment to TALE and CRISPR–dCas9 systems in mammalian cells and in…

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Publisher Correction: The chemical basis of ferroptosis

Posted on Jan 2nd, 2020 - By Marcus Conrad

Nature Chemical Biology, Published online: 02 January 2020; doi:10.1038/s41589-019-0434-zPublisher Correction: The chemical basis of…

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Allosteric mechanism for site-specific ubiquitination of FANCD2

Posted on Dec 23rd, 2019 - By Viduth K. Chaugule

Nature Chemical Biology, Published online: 23 December 2019; doi:10.1038/s41589-019-0426-zUBE2T adopts an allosteric activation mechanism to mediate site-specific ubiquitination of Fanconi anemia complex. Interaction with FANCL induces a cascade of conformational changes of UBE2T and leads to exposure of substrate-binding…

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Regulation of PTP1B activation through disruption of redox-complex formation

Posted on Dec 23rd, 2019 - By Avinash D. Londhe

Nature Chemical Biology, Published online: 23 December 2019; doi:10.1038/s41589-019-0433-0A transient interaction between 14-3-3ζ and a loop of PTP1B is detected following PTP1B inactivation by reversible…

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Dynamics of transcription–translation coordination tune bacterial indole signaling

Posted on Dec 23rd, 2019 - By Tianmin Wang

Nature Chemical Biology, Published online: 23 December 2019; doi:10.1038/s41589-019-0430-3The authors utilize fluorescence-activated cell sorting coupled with next-generation sequencing, as well as dynamic modeling, to study the molecular mechanism underlying indole signaling and reveal different roles of the two ends of tnaC in coordinating transcription and…

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An efficient gene knock-in strategy using 5′-modified double-stranded DNA donors with short homology arms

Posted on Dec 23rd, 2019 - By Yi Yu

Nature Chemical Biology, Published online: 23 December 2019; doi:10.1038/s41589-019-0432-1A simple and effective strategy is introduced to increase CRISPR–Cas9-mediated gene knock-in rates by using 5′-modified double-stranded DNA donors with short homology…

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Forging a new connection

Posted on Dec 16th, 2019 - By Caitlin Deane

Nature Chemical Biology, Published online: 16 December 2019; doi:10.1038/s41589-019-0439-7Forging a new…

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Artificial signaling in mammalian cells enabled by prokaryotic two-component system

Posted on Dec 16th, 2019 - By Alain Mazé

Nature Chemical Biology, Published online: 16 December 2019; doi:10.1038/s41589-019-0429-9Bacterial two-component signaling machinery has been reprogrammed for orthogonal signaling in mammalian cells that is triggered by small-molecule-mediated dimerization or ligand-induced GPCR/β-arrestin…

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Trashing transcription

Posted on Dec 16th, 2019 - By Yiyun Song

Nature Chemical Biology, Published online: 16 December 2019; doi:10.1038/s41589-019-0442-zTrashing…

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Dynamics of the context-specific translation arrest by chloramphenicol and linezolid

Posted on Dec 16th, 2019 - By Junhong Choi

Nature Chemical Biology, Published online: 16 December 2019; doi:10.1038/s41589-019-0423-2Single-molecule FRET technologies reveal the mechanism of sequence-specific translational inhibition induced by two antibiotics, chloramphenicol and linezolid, where aminoacyl-tRNA was repeatedly rejected from the A-site and failed to form a peptide…

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Tailor-made GPCRs

Posted on Dec 16th, 2019 - By R. Scott Prosser

Nature Chemical Biology, Published online: 16 December 2019; doi:10.1038/s41589-019-0427-yAn in silico directed evolution approach using first principles of allostery predicts the effects of protein sequence and structure variation on constitutive activity and ligand response in…

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Peptides skip a beat

Posted on Dec 16th, 2019 - By Mirella Bucci

Nature Chemical Biology, Published online: 16 December 2019; doi:10.1038/s41589-019-0441-0Peptides skip a…

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Mammalian signaling circuits from bacterial parts

Posted on Dec 16th, 2019 - By Xiaoyu Yang

Nature Chemical Biology, Published online: 16 December 2019; doi:10.1038/s41589-019-0436-xThe ability to engineer synthetic signaling networks has proven challenging for synthetic biology. A breakthrough design strategy shows that bacterial two-component-system-derived parts can be grafted into mammalian cells to create programmable phosphorylation…

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Engineering yeast phospholipid metabolism for de novo oleoylethanolamide production

Posted on Dec 16th, 2019 - By Yi Liu

Nature Chemical Biology, Published online: 16 December 2019; doi:10.1038/s41589-019-0431-2A combinatorial engineering strategy encompassing pathway regulation, heterologous enzymes and subcellular trafficking enables repurposing of the phospholipid biosynthetic pathway in Saccharomyces cerevisiae for the production of…

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A basic motif anchoring ISWI to nucleosome acidic patch regulates nucleosome spacing

Posted on Dec 9th, 2019 - By Hai T. Dao

Nature Chemical Biology, Published online: 09 December 2019; doi:10.1038/s41589-019-0413-4A photocrosslinking-based nucleosome profiling approach is used to identify a conserved basic motif in the ISWI remodeler SNF2h that anchors it to the acidic patch of nucleosome and enables nucleosome sliding…

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Accurate annotation of human protein-coding small open reading frames

Posted on Dec 9th, 2019 - By Thomas F. Martinez

Nature Chemical Biology, Published online: 09 December 2019; doi:10.1038/s41589-019-0425-0An improved workflow combining de novo transcriptome assembly and Ribo-seq validated by cellular antigen display is developed to maximize small peptide discovery, leading to identification of thousands of unannotated protein-coding…

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CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing’s sarcoma

Posted on Dec 9th, 2019 - By Nathan T. Ross

Nature Chemical Biology, Published online: 09 December 2019; doi:10.1038/s41589-019-0424-1The RNA endonuclease CPSF3 was identified as the cellular efficacy target of the small molecule JTE-607, revealing pre-mRNA processing as a vulnerability in cancers such as Ewing’s sarcoma that are characterized by aberrant…

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Molecular glue concept solidifies

Posted on Dec 9th, 2019 - By Kheewoong Baek

Nature Chemical Biology, Published online: 09 December 2019; doi:10.1038/s41589-019-0414-3Molecular-glue-mediated proximity-induced degradation now allows unprecedented therapeutic targeting of previously undruggable proteins. Structures showing how aryl-sulfonamides mediate recruitment of the splicing factor RBM39 to the E3 CRL4DCAF15 broaden the mechanistic principles by which molecular glues target…

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Discovery of a first-in-class EZH2 selective degrader

Posted on Dec 9th, 2019 - By Anqi Ma

Nature Chemical Biology, Published online: 09 December 2019; doi:10.1038/s41589-019-0421-4A hydrophobic tagging method is used to develop a selective degrader for the chromatin regulator EZH2, which inhibits proliferation of triple-negative breast cancer cell lines in vitro and in…

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Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex

Posted on Dec 9th, 2019 - By Dirksen E. Bussiere

Nature Chemical Biology, Published online: 09 December 2019; doi:10.1038/s41589-019-0411-6The crystal and cryo-electron microscopy structure analysis of the DCAF15–DDB1–DDA1–indisulam–RBM39 complex revealed the detailed mechanism of action of indisulam-induced RBM39 degradation and defined an α-helical degron motif in…

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Processing for destruction

Posted on Dec 9th, 2019 - By Michael A. Erb

Nature Chemical Biology, Published online: 09 December 2019; doi:10.1038/s41589-019-0428-xPhenotypic screening is an engine of discovery for bioactive small molecules and can unravel novel mechanisms and pathways controlling cellular physiology. A recent study reveals the CPSF complex as a pharmacologically tractable target of JTE-607 and context-specific cancer…

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Differential roles of human PUS10 in miRNA processing and tRNA pseudouridylation

Posted on Dec 9th, 2019 - By Jinghui Song

Nature Chemical Biology, Published online: 09 December 2019; doi:10.1038/s41589-019-0420-5PUS10 exhibits two different functions: one is to promote miRNA biogenesis in a catalytically independent manner; the other is to install pseudouridine modification in tRNAs in a catalytically dependent…

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Computational design of G Protein-Coupled Receptor allosteric signal transductions

Posted on Dec 2nd, 2019 - By Kuang-Yui Michael Chen

Nature Chemical Biology, Published online: 02 December 2019; doi:10.1038/s41589-019-0407-2A computational approach for designing GPCRs with new signaling functions including allosteric signaling properties yielded D2 receptor variants with predictable G-protein signaling responses, some with enhanced potency and responses to…

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Guided nuclear exploration increases CTCF target search efficiency

Posted on Dec 2nd, 2019 - By Anders S. Hansen

Nature Chemical Biology, Published online: 02 December 2019; doi:10.1038/s41589-019-0422-3Single-particle tracking and mathematical modeling methods reveal the searching mechanism of CTCF for its cognate sites on DNA. An RNA-binding region in CTCF mediates its trapping in small zones and increases its target search…

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Targeting the interaction of AIMP2-DX2 with HSP70 suppresses cancer development

Posted on Dec 2nd, 2019 - By Semi Lim

Nature Chemical Biology, Published online: 02 December 2019; doi:10.1038/s41589-019-0415-2The cellular stability of an oncogenic factor, AIMP2-DX2, is increased via association with HSP70. Interference with this interaction by a small-molecule compound promotes ubiquitin-mediated degradation of AIMP2-DX2 and reduces cancer cell…

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Resilient living materials built by printing bacterial spores

Posted on Dec 2nd, 2019 - By Lina M. González

Nature Chemical Biology, Published online: 02 December 2019; doi:10.1038/s41589-019-0412-53D printing agarose hydrogels embedded with Bacillus subtilis spores produce custom-shaped materials that are resistant to environmental stresses, while the bacteria maintain the ability to germinate on the surface and respond to…

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A computational framework to explore large-scale biosynthetic diversity

Posted on Nov 25th, 2019 - By Jorge C. Navarro-Muñoz

Nature Chemical Biology, Published online: 25 November 2019; doi:10.1038/s41589-019-0400-9Two bioinformatic tools, BiG-SCAPE and CORASON, enable sequence similarity network and phylogenetic analysis of gene clusters and their families across hundreds of strains and in large datasets, leading to the discovery of new natural…

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Engineering a nicotinamide mononucleotide redox cofactor system for biocatalysis

Posted on Nov 25th, 2019 - By William B. Black

Nature Chemical Biology, Published online: 25 November 2019; doi:10.1038/s41589-019-0402-7Redesign of a glucose dehydrogenase to use nicotinamide mononucleotide (NMN+) instead of NAD(P)+ enables the development of a noncanonical cofactor system that can be used to support redox chemistries both in vitro and in Escherichia…

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Global targeting of functional tyrosines using sulfur-triazole exchange chemistry

Posted on Nov 25th, 2019 - By Heung Sik Hahm

Nature Chemical Biology, Published online: 25 November 2019; doi:10.1038/s41589-019-0404-5Sulfur-triazole exchange (SuTEx) chemistry is a tunable platform for covalent chemoproteomic probes that selectively target tyrosines, used to identify residues with enhanced nucleophilicity and monitor activation of phosphotyrosine…

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Discovery of an antivirulence compound that reverses <i>β</i>-lactam resistance in MRSA

Posted on Nov 25th, 2019 - By Omar M. El-Halfawy

Nature Chemical Biology, Published online: 25 November 2019; doi:10.1038/s41589-019-0401-8A potent inhibitor of the MRSA virulence regulator, GraR, reverses methicillin resistance, inhibits biofilm formation, limits bacterial survival in macrophages and attenuates virulence in vitro, synergizing with cationic antimicrobial…

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Axonal dispatch of iron in neuronal signaling

Posted on Nov 18th, 2019 - By Peng Lei

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0394-3The regulation of brain iron homeostasis, previously thought to be cell autonomous and modulated by local factors in the interstitial fluid, is reported by Wang et al. to be strongly influenced by axonal transport of iron in an activity-dependent and unidirectional manner between functionally associated regions. The supply of iron from the ventral hippocampus to the middle prefrontal cortex subserved an…

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Choosing a mating site

Posted on Nov 18th, 2019 - By Mirella Bucci

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0418-zChoosing a mating…

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Iodine goes viral

Posted on Nov 18th, 2019 - By Caitlin Deane

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0416-1Iodine goes…

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Solo act revealed to be duet

Posted on Nov 18th, 2019 - By Mohamed Atta

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0406-3The last step of archaeosine biosynthesis was found to involve two enzymes, the previously known ArcS with lysine transfer activity and a novel identified radical SAM enzyme named…

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Cutting actin with light

Posted on Nov 18th, 2019 - By Qian Chen

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0410-7Actin cytoskeletal structures are essential for many cellular processes, and cofilin is a key protein for the assembly of these highly dynamic structures. A new cofilin construct enables precise optogenetic control of actin assembly in live…

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Identification of a radical SAM enzyme involved in the synthesis of archaeosine

Posted on Nov 18th, 2019 - By Takashi Yokogawa

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0390-7Euryarchaeal ArcS alone cannot produce G+-containing tRNA but works as a lysine transferase to produce a lysine adduct intermediate, which finally forms G+-containing tRNA in the presence of a newly identified SAM enzyme,…

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The chemical basis of ferroptosis

Posted on Nov 18th, 2019 - By Marcus Conrad

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0408-1This Perspective focuses on the chemical basis of ferroptotic cell death, discussing the prominent role of spontaneous chemical reactions, how they depend on enzyme-catalyzed processes and how to exploit this interplay for therapeutic…

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Site-specific acylation of a bacterial virulence regulator attenuates infection

Posted on Nov 18th, 2019 - By Zhenrun J. Zhang

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0392-5Microbiota-derived butyrate acylation of the key Salmonella enterica transcriptional regulator HilA attenuates virulence of the bacteria, blocking invasion of epithelial cells in vitro and dissemination in…

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Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15

Posted on Nov 4th, 2019 - By Tyler B. Faust

Nature Chemical Biology, Published online: 04 November 2019; doi:10.1038/s41589-019-0378-3Cryo-EM and crystal structural analysis of DDB1–DCAF15–DDA1 in complex with E7820 and RBM39 reveal that aryl-sulfonamides reshape the surface of the cullin RING ligase substrate receptor DCAF15 to bind and degrade the splicing factor…

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Two-site recognition of <i>Staphylococcus aureus</i> peptidoglycan by lysostaphin SH3b

Posted on Nov 4th, 2019 - By Luz S. Gonzalez-Delgado

Nature Chemical Biology, Published online: 04 November 2019; doi:10.1038/s41589-019-0393-4A structural look at the interaction between the SH3b domain of the peptidoglycan endopeptidase lysostaphin and the target for its antistaphylococcal activity, peptidoglycan, reveals a mechanism of bacterial cell wall…

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De novo-designed translation-repressing riboregulators for multi-input cellular logic

Posted on Nov 4th, 2019 - By Jongmin Kim

Nature Chemical Biology, Published online: 04 November 2019; doi:10.1038/s41589-019-0388-1Two programmable riboregulator systems, based on toehold and three-way junction RNA motifs, were designed and validated as robust translational repressors in cells and applied for the construction of logic…

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Uncoupling of PARP1 trapping and inhibition using selective PARP1 degradation

Posted on Oct 28th, 2019 - By Shuai Wang

Nature Chemical Biology, Published online: 28 October 2019; doi:10.1038/s41589-019-0379-2Small molecules that achieve selective PARP1 degradation were developed that block both the catalytic activity and scaffolding effects of PARP1, enabling the decoupling of PARP1 inhibition and PARP1…

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Structure of an allosteric modulator bound to the CB1 cannabinoid receptor

Posted on Oct 28th, 2019 - By Zhenhua Shao

Nature Chemical Biology, Published online: 28 October 2019; doi:10.1038/s41589-019-0387-2A crystal structure of the GPCR target of endocannabinoid signaling lipids and drugs, CB1, bound to a negative allosteric modulator (NAM) and an agonist, shows that the NAM binds to a membrane-embedded site reminiscent of the binding site of…

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Author Correction: MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG

Posted on Oct 23rd, 2019 - By Louise Fets

Nature Chemical Biology, Published online: 23 October 2019; doi:10.1038/s41589-019-0409-0Author Correction: MCT2 mediates concentration-dependent inhibition of glutamine metabolism by…

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Disorder guides order

Posted on Oct 21st, 2019 - By Yiyun Song

Nature Chemical Biology, Published online: 21 October 2019; doi:10.1038/s41589-019-0398-zDisorder guides…

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Higher-order epistasis shapes the fitness landscape of a xenobiotic-degrading enzyme

Posted on Oct 21st, 2019 - By Gloria Yang

Nature Chemical Biology, Published online: 21 October 2019; doi:10.1038/s41589-019-0386-3Ancestral protein reconstruction followed by biochemical and structural analyses characterizes the evolutionary trajectory of methyl-parathion hydrolase from an ancestral dihydrocoumarin hydrolase through the accumulation of five key…

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Extracellular phosphorylation in axon pathfinding

Posted on Oct 21st, 2019 - By Patricia T. Yam

Nature Chemical Biology, Published online: 21 October 2019; doi:10.1038/s41589-019-0383-6The growth and guidance of axons dictate their trajectories and are critical for neural-circuit formation. Research in this issue uncovers a new mechanism for regulation of axon growth and guidance that acts via extracellular phosphorylation of a…

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An inside job

Posted on Oct 21st, 2019 - By Caitlin Deane

Nature Chemical Biology, Published online: 21 October 2019; doi:10.1038/s41589-019-0395-2An inside…

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Molecular basis for the P450-catalyzed C–N bond formation in indolactam biosynthesis

Posted on Oct 21st, 2019 - By Fei He

Nature Chemical Biology, Published online: 21 October 2019; doi:10.1038/s41589-019-0380-9Structural and functional analyses of two cytochrome P450 monooxygenases reveal how they catalyze C–N bond formation via a diradical mechanism and are able to accommodate a variety of substrates to form either indolactam or tricyclic…

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Long-range tedatmporal coordination of gene expression in synthetic microbial consortia

Posted on Oct 14th, 2019 - By Jae Kyoung Kim

Nature Chemical Biology, Published online: 14 October 2019; doi:10.1038/s41589-019-0372-9Synthetic microbial consortia were applied to demonstrate that oscillatory gene expression in a bacterial population can be propagated over longer distances by activating a localized positive feedback…

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Structural basis of sequence-specific Holliday junction cleavage by MOC1

Posted on Oct 14th, 2019 - By Huajian Lin

Nature Chemical Biology, Published online: 14 October 2019; doi:10.1038/s41589-019-0377-4Crystal structural and biochemical analysis of the chloroplast-localized Holliday junction (HJ) resolvase MOC1 in Zea mays reveals that ZmMOC1 uses a unique β-hairpin structure and a two-metal ion catalysis mechanism to recognize and cleave…

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