Drugging viral factories

Posted on Aug 23rd, 2021 - By Majda Bratovič

Nature Chemical Biology, Published online: 23 August 2021; doi:10.1038/s41589-021-00872-wDrugging viral…

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Put another ring on it

Posted on Aug 23rd, 2021 - By Caitlin Deane

Nature Chemical Biology, Published online: 23 August 2021; doi:10.1038/s41589-021-00871-xPut another ring on…

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Go with the FLOE

Posted on Aug 23rd, 2021 - By Ross Cloney

Nature Chemical Biology, Published online: 23 August 2021; doi:10.1038/s41589-021-00869-5Go with the…

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Ditching the chaperone

Posted on Aug 23rd, 2021 - By Grant Miura

Nature Chemical Biology, Published online: 23 August 2021; doi:10.1038/s41589-021-00870-yDitching the…

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Bifunctional small molecules that mediate the degradation of extracellular proteins

Posted on Aug 19th, 2021 - By David F. Caianiello

Nature Chemical Biology, Published online: 19 August 2021; doi:10.1038/s41589-021-00851-1Bifunctional ‘MoDE-A’ molecules, which contain ligands that bind to an extracellular protein and carbohydrate residues that recruit it to the asialoglycoprotein receptor, mediate cellular uptake and lysosomal turnover of target…

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Lysosome-targeting chimeras evolve

Posted on Aug 19th, 2021 - By Joshiawa Paulk

Nature Chemical Biology, Published online: 19 August 2021; doi:10.1038/s41589-021-00835-1LYTACs induce selective degradation of extracellular proteins by recruiting them to cellular receptors that mediate delivery to the lysosome. Recent development of GalNAc-LYTACs and MoDE-As targeting the liver-specific ASGPR enables cell-type-restricted lysosomal protein degradation and reveals new LYTAC design…

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Dan Salah Tawfik (1955–2021)

Posted on Aug 16th, 2021 - By Paola Laurino

Nature Chemical Biology, Published online: 16 August 2021; doi:10.1038/s41589-021-00864-wDan Tawfik suddenly left us on 4 May, 2021. His scientific intuition led him to articulate, and solve, many key questions related to protein chemistry and molecular evolution. Although science, particularly for his students, postdoctoral fellows and colleagues, is dimmer after his loss, his legacy will…

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Structures and function of the amino acid polymerase cyanophycin synthetase

Posted on Aug 12th, 2021 - By Itai Sharon

Nature Chemical Biology, Published online: 12 August 2021; doi:10.1038/s41589-021-00854-yStructures of three cyanophycin synthetases reveal how the constituent glutathione synthetase and muramyl ligase-like domains cooperate to make cyanophycin, a poly-aspartate chain with arginine residues attached to the sidechains by isopeptide…

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Addendum: Cryptic phosphorylation in nucleoside natural product biosynthesis

Posted on Aug 11th, 2021 - By Matthew M. Draelos

Nature Chemical Biology, Published online: 11 August 2021; doi:10.1038/s41589-021-00867-7Addendum: Cryptic phosphorylation in nucleoside natural product…

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Accelerated RNA detection using tandem CRISPR nucleases

Posted on Aug 5th, 2021 - By Tina Y. Liu

Nature Chemical Biology, Published online: 05 August 2021; doi:10.1038/s41589-021-00842-2Deploying two unrelated CRISPR nucleases in tandem, with multiplexed CRISPR RNAs and a chemically stabilized activator, creates a simple, one-step assay that can rapidly detect attomolar concentrations of RNA without needing target…

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A giant ubiquitin ligase

Posted on Aug 3rd, 2021 - By Hidde Ploegh

Nature Chemical Biology, Published online: 03 August 2021; doi:10.1038/s41589-021-00860-0The structure of a giant ubiquitin E3 ligase sheds light on its activation in a substrate-dependent manner and shows how a single E3 enzyme uses distinct recognition modules to confer substrate…

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A topological switch in CFTR modulates channel activity and sensitivity to unfolding

Posted on Aug 2nd, 2021 - By Daniel Scholl

Nature Chemical Biology, Published online: 02 August 2021; doi:10.1038/s41589-021-00844-0The cystic fibrosis transmembrane conductance regulator anion channel can adopt an alternate conformation of its nucleotide-binding domain, which affects channel activity and, under certain conditions, leads to unfolding and protein…

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Designer membraneless organelles sequester native factors for control of cell behavior

Posted on Aug 2nd, 2021 - By Mikael V. Garabedian

Nature Chemical Biology, Published online: 02 August 2021; doi:10.1038/s41589-021-00840-4Controlled assembly of synthetic intracellular condensates from engineered disordered proteins enables control of cellular activities such as proliferation and division through recruitment, sequestration and insulation of endogenous client…

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Insulating proteins drop by drop

Posted on Aug 2nd, 2021 - By Ulrich Krauss

Nature Chemical Biology, Published online: 02 August 2021; doi:10.1038/s41589-021-00846-yLiquid–liquid phase separation, yielding membraneless organelles, allows for the sequestration and functional insulation of cellular proteins. A modularly built, synthetic membraneless organelle platform enables efficient control over endogenous cellular activities by knockdown of protein function or controlled protein…

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Disorder is a critical component of lipoprotein sorting in Gram-negative bacteria

Posted on Jul 29th, 2021 - By Jessica El Rayes

Nature Chemical Biology, Published online: 29 July 2021; doi:10.1038/s41589-021-00845-zApproximately half of lipoproteins destined to the Escherichia coli outer membrane display intrinsically disordered linker peptides at their N termini, which are required for optimal trafficking by the Lol lipoprotein sorting…

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Metabolic engineering strategies to enable microbial utilization of C1 feedstocks

Posted on Jul 26th, 2021 - By Wei Jiang

Nature Chemical Biology, Published online: 26 July 2021; doi:10.1038/s41589-021-00836-0A survey of natural metabolic pathways for C1 substrates (methane, methanol, carbon dioxide, and carbon monoxide) highlights past efforts and recent progress, and informs future opportunities to create synthetic C1-utilizing…

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Prospecting for natural products by genome mining and microcrystal electron diffraction

Posted on Jul 26th, 2021 - By Lee Joon Kim

Nature Chemical Biology, Published online: 26 July 2021; doi:10.1038/s41589-021-00834-2Combined use of microcrystal electron diffraction and genome mining for biosynthetic gene clusters enables the rapid structural elucidation of natural products, including a newly discovered 2-pyridone compound and a revised structure of…

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Untying knots with force

Posted on Jul 26th, 2021 - By Pan T. X. Li

Nature Chemical Biology, Published online: 26 July 2021; doi:10.1038/s41589-021-00856-wRNA knot-like structures function as an efficient physical barrier to RNA exoribonucleases. Single-molecule mechanical manipulation is used to unfold these structures and unravel the cause of their unusual mechanical resistance from a different…

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Central dogma, redefined

Posted on Jul 26th, 2021 - By Yiyun Song

Nature Chemical Biology, Published online: 26 July 2021; doi:10.1038/s41589-021-00850-2Central dogma,…

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A molecular shape-shifter

Posted on Jul 26th, 2021 - By Karin Kühnel

Nature Chemical Biology, Published online: 26 July 2021; doi:10.1038/s41589-021-00848-wA molecular…

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Picking off persisters

Posted on Jul 26th, 2021 - By Caitlin Deane

Nature Chemical Biology, Published online: 26 July 2021; doi:10.1038/s41589-021-00847-xPicking off…

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Mucin tuning

Posted on Jul 26th, 2021 - By Philip Lössl

Nature Chemical Biology, Published online: 26 July 2021; doi:10.1038/s41589-021-00849-9Mucin…

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HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain

Posted on Jul 22nd, 2021 - By Daniel B. Grabarczyk

Nature Chemical Biology, Published online: 22 July 2021; doi:10.1038/s41589-021-00831-5The full-length structure of HUWE1 reveals the bipartite organization of a giant E3 ubiquitin ligase, comprising a catalytic HECT domain and a large, ring-shaped scaffold that provides docking sites for various substrates and regulates E3…

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Mechanical strength of RNA knot in Zika virus protects against cellular defenses

Posted on Jul 12th, 2021 - By Meng Zhao

Nature Chemical Biology, Published online: 12 July 2021; doi:10.1038/s41589-021-00829-zA knot-like RNA from Zika virus is shown to evade digestion by host RNases through its extreme resistance to mechanical unfolding. Weakening the knot mechanically or reducing the likelihood of knot formation lowers the RNase…

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Imaging and targeting LOX-mediated tissue remodeling with a reactive collagen peptide

Posted on Jul 12th, 2021 - By Matthew R. Aronoff

Nature Chemical Biology, Published online: 12 July 2021; doi:10.1038/s41589-021-00830-6Collagen cross-linking, mediated by lysyl oxidases (LOX), is critical for the stability of the extracellular matrix. Aldehyde-reactive sensors and collagen peptide probes for monitoring LOX activity enable direct in vivo imaging of collagen…

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K29-linked ubiquitin signaling regulates proteotoxic stress response and cell cycle

Posted on Jul 8th, 2021 - By Yuanyuan Yu

Nature Chemical Biology, Published online: 08 July 2021; doi:10.1038/s41589-021-00823-5A linkage-specific tool for K29-linked polyubiquitin was developed, enabling the discovery that K29-linked ubiquitination participates in multiple cellular pathways, including the proteotoxic stress response and cell cycle…

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Linking K29-Ub chains to biology

Posted on Jul 8th, 2021 - By Sven M. Lange

Nature Chemical Biology, Published online: 08 July 2021; doi:10.1038/s41589-021-00833-3Different ubiquitin chain types serve as distinct cellular signals. A new synthetic antigen-binding fragment, sAB-K29, specifically recognizes K29-linked diubiquitin and links K29 chains to proteotoxic stress and their accumulation in midbodies during…

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Full speed AHEAD in antibody discovery

Posted on Jul 1st, 2021 - By Paul R. Sargunas

Nature Chemical Biology, Published online: 01 July 2021; doi:10.1038/s41589-021-00838-yCurrent antibody discovery technologies are limited in terms of their efficacy, accessibility, and scalability. The AHEAD system addresses these limitations by presenting an accelerated evolution workflow for antibody engineering that combines autonomous gene diversification with protein display…

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Author Correction: Selective inhibitors of mTORC1 activate 4EBP1 and suppress tumor growth

Posted on Jun 29th, 2021 - By Bianca J. Lee

Nature Chemical Biology, Published online: 29 June 2021; doi:10.1038/s41589-021-00843-1Author Correction: Selective inhibitors of mTORC1 activate 4EBP1 and suppress tumor…

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A tonic for <i>moonshine</i>

Posted on Jun 25th, 2021 - By Grant Miura

Nature Chemical Biology, Published online: 25 June 2021; doi:10.1038/s41589-021-00826-2A tonic for…

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RNA structure probing uncovers RNA structure-dependent biological functions

Posted on Jun 25th, 2021 - By Xi-Wen Wang

Nature Chemical Biology, Published online: 25 June 2021; doi:10.1038/s41589-021-00805-7This Review summarizes the recent technical advances in probing RNA secondary structures and discusses their connection with RNA regulatory functions in various biological processes and future directions in RNA structure-probing…

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Design and build microbiomes

Posted on Jun 25th, 2021 - By Ross Cloney

Nature Chemical Biology, Published online: 25 June 2021; doi:10.1038/s41589-021-00828-0Design and build…

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Say yes to the NOS

Posted on Jun 25th, 2021 - By Caitlin Deane

Nature Chemical Biology, Published online: 25 June 2021; doi:10.1038/s41589-021-00825-3Say yes to the…

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Reshape to survive

Posted on Jun 25th, 2021 - By Majda Bratovič

Nature Chemical Biology, Published online: 25 June 2021; doi:10.1038/s41589-021-00827-1Reshape to…

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Rapid generation of potent antibodies by autonomous hypermutation in yeast

Posted on Jun 24th, 2021 - By Alon Wellner

Nature Chemical Biology, Published online: 24 June 2021; doi:10.1038/s41589-021-00832-4Autonomous hypermutation yeast surface display (AHEAD) mimics the process of somatic hypermutation in animals to enable the rapid in vitro evolution of antibodies, including nanobodies targeting the RBD of…

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Selective inhibitors of mTORC1 activate 4EBP1 and suppress tumor growth

Posted on Jun 24th, 2021 - By Bianca J. Lee

Nature Chemical Biology, Published online: 24 June 2021; doi:10.1038/s41589-021-00813-7Design of a bivalent inhibitor containing an ATP-competitive moiety and rapamycin-modified FRB binding ligand that selectively inhibits mTORC1 results in potent and durable inhibition of 4EBP1 phosphorylation and cell proliferation in vitro and in…

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Split-personality inhibitors

Posted on Jun 24th, 2021 - By Carson C. Thoreen

Nature Chemical Biology, Published online: 24 June 2021; doi:10.1038/s41589-021-00820-8A rationally designed class of mTORC1 inhibitors combines the selectivity of rapamycin with the potency of mTOR kinase…

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Small-molecule inhibitors targeting Polycomb repressive complex 1 RING domain

Posted on Jun 21st, 2021 - By Shirish Shukla

Nature Chemical Biology, Published online: 21 June 2021; doi:10.1038/s41589-021-00815-5Fragment screening and medicinal chemistry optimization led to development of a small-molecule inhibitor of RING1B–BMI1 E3 ligase, blocking the H2A ubiquitination activity of the Polycomb repressive complex 1 and inducing differentiation in leukemia…

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Predictable control of RNA lifetime using engineered degradation-tuning RNAs

Posted on Jun 21st, 2021 - By Qi Zhang

Nature Chemical Biology, Published online: 21 June 2021; doi:10.1038/s41589-021-00816-4Degradation-tuning RNAs (dtRNAs) have the capacity to increase and decrease RNA stability in vivo and in vitro. Appending these modules to transcripts allows fine tuning of circuit dynamics, CRISPR interference and paper-based viral…

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Fighting PRC1 via the RING

Posted on Jun 21st, 2021 - By Joshua P. Plotnik

Nature Chemical Biology, Published online: 21 June 2021; doi:10.1038/s41589-021-00819-1Over the past two decades, inhibitors of the polycomb repressor complex (PRC) have been driven from bench to bedside. New chemical compounds targeting the RING1B in polycomb repressor complex 1 (PRC1) add important tools to regulate polycomb…

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Transcriptional processing of an unnatural base pair by eukaryotic RNA polymerase II

Posted on Jun 17th, 2021 - By Juntaek Oh

Nature Chemical Biology, Published online: 17 June 2021; doi:10.1038/s41589-021-00817-3Structural biology, computational biology and biochemical analysis revealed the molecular mechanism of transcriptional processing of unnatural base pairs selectively recognized by cellular RNA…

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Handling heme with care

Posted on Jun 8th, 2021 - By Breann L. Brown

Nature Chemical Biology, Published online: 08 June 2021; doi:10.1038/s41589-021-00821-7Heme-containing proteins support a broad range of cellular functions. A new crystal structure explains how an integral-membrane heme lyase attaches the hydrophobic heme to soluble…

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Co-occurrence of enzyme domains guides the discovery of an oxazolone synthetase

Posted on Jun 7th, 2021 - By Tristan de Rond

Nature Chemical Biology, Published online: 07 June 2021; doi:10.1038/s41589-021-00808-4A genome-mining approach targeted to enzyme domains that co-occur in a single protein (CO-ED) facilitates the discovery and characterization of an oxazolone synthetase involved in the biosynthesis of a series of oxazolone-containing natural…

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Differential regulation of single microtubules and bundles by a three-protein module

Posted on Jun 3rd, 2021 - By Nandini Mani

Nature Chemical Biology, Published online: 03 June 2021; doi:10.1038/s41589-021-00800-yReconstitution studies reveal design principles by which a minimal 3-protein module differentially regulates the dynamics of spatially proximal crosslinked and noncrosslinked microtubules, mimicking microtubule array dynamics in the mitotic…

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Modification of cell wall polysaccharide guides cell division in <i>Streptococcus mutans</i>

Posted on May 27th, 2021 - By Svetlana Zamakhaeva

Nature Chemical Biology, Published online: 27 May 2021; doi:10.1038/s41589-021-00803-9Glycerol phosphate modifications of cell wall carbohydrates localize regulators of cell division in Streptococcus…

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Undermodification cues division

Posted on May 27th, 2021 - By Malcolm E. Winkler

Nature Chemical Biology, Published online: 27 May 2021; doi:10.1038/s41589-021-00818-2Extracellular peptidoglycan-linked polysaccharide modifications mediate cell morphology, division, and autolysis in some Gram-positive bacterial pathogens. A new study shows that the degree and location of a specific modification controls peptidoglycan hydrolysis and placement of the axis of cell…

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Author Correction: Enzymes knuckle down to the job

Posted on May 27th, 2021 - By Paul H. Walton

Nature Chemical Biology, Published online: 27 May 2021; doi:10.1038/s41589-021-00824-4Author Correction: Enzymes knuckle down to the…

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Switching on the CAR

Posted on May 25th, 2021 - By Yiyun Song

Nature Chemical Biology, Published online: 25 May 2021; doi:10.1038/s41589-021-00812-8Switching on the…

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An oxPEdition into cell death

Posted on May 25th, 2021 - By Philip Lössl

Nature Chemical Biology, Published online: 25 May 2021; doi:10.1038/s41589-021-00811-9An oxPEdition into cell…

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Peering into the cellular cycle

Nature Chemical Biology, Published online: 25 May 2021; doi:10.1038/s41589-021-00814-6The development of chemical tools and small-molecule inhibitors enables the resolution of critical cellular processes with high spatial and temporal…

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Compromised autophagy

Posted on May 25th, 2021 - By Caitlin Deane

Nature Chemical Biology, Published online: 25 May 2021; doi:10.1038/s41589-021-00809-3Compromised…

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Shape matching

Posted on May 25th, 2021 - By Karin Kühnel

Nature Chemical Biology, Published online: 25 May 2021; doi:10.1038/s41589-021-00810-wShape…

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Sulfopin is a covalent inhibitor of Pin1 that blocks Myc-driven tumors in vivo

Posted on May 10th, 2021 - By Christian Dubiella

Nature Chemical Biology, Published online: 10 May 2021; doi:10.1038/s41589-021-00786-7The development of Sulfopin, a highly selective and potent, covalent Pin1 inhibitor that phenocopies Pin1 knockout and regresses tumors in murine and zebrafish models of neuroblastoma as well as in a pancreatic cancer mouse…

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Rethinking sustainability through synthetic biology

Posted on May 10th, 2021 - By Vamsi Kovelakuntla

Nature Chemical Biology, Published online: 10 May 2021; doi:10.1038/s41589-021-00804-8The use of bacterial biofilms provides a bioplastic that is biodegradable, water processable, and coatable, opening new avenues for plastic…

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Architecture of the membrane-bound cytochrome <i>c</i> heme lyase CcmF

Posted on May 6th, 2021 - By Anton Brausemann

Nature Chemical Biology, Published online: 06 May 2021; doi:10.1038/s41589-021-00793-8The structure of the heme lyase CcmF, an integral membrane protein, reveals a cavity opening toward the extracellular side to receive heme groups from the chaperone CcmE and a surface groove for guiding the substrate protein during heme…

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Genetically encoded multivalent liquid glycan array displayed on M13 bacteriophage

Posted on May 6th, 2021 - By Mirat Sojitra

Nature Chemical Biology, Published online: 06 May 2021; doi:10.1038/s41589-021-00788-5Liquid glycan arrays (LiGAs), presented on M13 bacteriophage surface proteins through bioorthogonal chemistry, link surface glycans to genetic barcodes in phage DNA, enabling lectin–glycan interaction profiling by DNA…

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Circularly permuted LOV2 as a modular photoswitch for optogenetic engineering

Posted on May 6th, 2021 - By Lian He

Nature Chemical Biology, Published online: 06 May 2021; doi:10.1038/s41589-021-00792-9A set of LOV2 circular permutants (cpLOV2) have been engineered to expand the existing optogenetic toolbox. cpLOV2 enables the design of both ON- and OFF-switches to control cell signaling, gene expression, cell fate and cancer…

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A molecular trap inside microtubules probes luminal access by soluble proteins

Posted on May 3rd, 2021 - By Yuta Nihongaki

Nature Chemical Biology, Published online: 03 May 2021; doi:10.1038/s41589-021-00791-wA chemically inducible technique for trapping cytosolic proteins in microtubules (MTs) in cells reveals that soluble proteins can enter the MT lumen by diffusion, while proteins forming a complex with tubulins can be incorporated at MT plus…

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ABHD17 regulation of plasma membrane palmitoylation and N-Ras-dependent cancer growth

Posted on Apr 29th, 2021 - By Jarrett R. Remsberg

Nature Chemical Biology, Published online: 29 April 2021; doi:10.1038/s41589-021-00785-8ABD957 is a potent and selective inhibitor of the ABHD17 family of depalmitoylases that disrupts N-Ras signaling in human acute myeloid leukemia cells and can synergize with MEK…

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A stop sign for RAS trafficking

Posted on Apr 29th, 2021 - By Tian Qiu

Nature Chemical Biology, Published online: 29 April 2021; doi:10.1038/s41589-021-00789-4N-Ras lipidation cycling is known to regulate its trafficking and function. A new S-depalmitoylation inhibitor induces N-Ras membrane mislocalization, providing insights into N-Ras function and laying the foundation for a new cancer therapeutic…

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Focal assembly

Posted on Apr 26th, 2021 - By Yiyun Song

Nature Chemical Biology, Published online: 26 April 2021; doi:10.1038/s41589-021-00797-4Focal…

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Guiding light

Posted on Apr 26th, 2021 - By Grant Miura

Nature Chemical Biology, Published online: 26 April 2021; doi:10.1038/s41589-021-00794-7Guiding…

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Designing stable DNAzymes

Posted on Apr 26th, 2021 - By Ross Cloney

Nature Chemical Biology, Published online: 26 April 2021; doi:10.1038/s41589-021-00796-5Designing stable…

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Crossing boundaries

Posted on Apr 26th, 2021 - By Karin Kühnel

Nature Chemical Biology, Published online: 26 April 2021; doi:10.1038/s41589-021-00795-6Crossing…

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Engineering AraC to make it responsive to light instead of arabinose

Posted on Apr 26th, 2021 - By Edoardo Romano

Nature Chemical Biology, Published online: 26 April 2021; doi:10.1038/s41589-021-00787-6Engineering of a blue light-inducible AraC dimerization system in E. coli permits light-dependent, rather than arabinose-based, regulation of gene expression from standard PBAD promoters, enabling temporal and spatial control of bacterial…

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Substrate-biased activity-based probes identify proteases that cleave receptor CDCP1

Posted on Apr 15th, 2021 - By Thomas Kryza

Nature Chemical Biology, Published online: 15 April 2021; doi:10.1038/s41589-021-00783-wA substrate-biased activity-based probe technology was developed to enable relatively facile identification of proteases responsible for specific proteolytic events in complex biological milieu, revealing that urokinase regulates CDCP1…

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Genome-wide screens uncover KDM2B as a modifier of protein binding to heparan sulfate

Posted on Apr 12th, 2021 - By Ryan J. Weiss

Nature Chemical Biology, Published online: 12 April 2021; doi:10.1038/s41589-021-00776-9A CRISPR–Cas9 screen combined with heparan sulfate (HS)-binding reagents identifies genes involved in HS biosynthesis and assembly and reveals the unexpected role of histone demethylase KDM2B in regulating HS presentation on the cell…

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Hydrogel-based biocontainment of bacteria for continuous sensing and computation

Posted on Apr 5th, 2021 - By Tzu-Chieh Tang

Nature Chemical Biology, Published online: 05 April 2021; doi:10.1038/s41589-021-00779-6A dual-layer encapsulation approach provides physical containment of genetically modified bacteria (especially when combined with chemical containment) while also protecting them from environmental stressors and maintaining their sensing…

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The HaloTag as a general scaffold for far-red tunable chemigenetic indicators

Posted on Apr 1st, 2021 - By Claire Deo

Nature Chemical Biology, Published online: 01 April 2021; doi:10.1038/s41589-021-00775-wCombining the self-labeling HaloTag protein with synthetic environmentally sensitive fluorophores provides a platform for the construction of bright, far-red fluorescent calcium and voltage sensors with tunable photophysical and chemical…

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LYTACs that engage the asialoglycoprotein receptor for targeted protein degradation

Posted on Mar 25th, 2021 - By Green Ahn

Nature Chemical Biology, Published online: 25 March 2021; doi:10.1038/s41589-021-00770-1Lysosome-targeting chimeras (LYTACs) based on glycan ligands of the asialoglycoprotein receptor facilitate the cell-specific targeting and turnover of proteins by lysosomal enzymes, expanding the scope of LYTAC-mediated targeted protein…

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Biomolecular condensates amplify mRNA decapping by biasing enzyme conformation

Posted on Mar 25th, 2021 - By Ryan W. Tibble

Nature Chemical Biology, Published online: 25 March 2021; doi:10.1038/s41589-021-00774-xAlterations in the interactions driving phase separation of the mRNA decapping complex led to conformational rearrangements in its active site, providing a mechanism to control whether substrate mRNA is stored or decapped in…

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Mining for mouth metabolites

Posted on Mar 25th, 2021 - By Amber M. Scharnow

Nature Chemical Biology, Published online: 25 March 2021; doi:10.1038/s41589-021-00784-9Genome mining of Streptococcus mutans clinical samples led to the identification of a structurally unique polyketide/non-ribosomal peptide, mutanofactin-697, that promotes biofilm formation. This study highlights the unexplored functional potential of secondary metabolites and opens new avenues for inhibiting pathogenic…

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Stamp it here

Posted on Mar 24th, 2021 - By Yiyun Song

Nature Chemical Biology, Published online: 24 March 2021; doi:10.1038/s41589-021-00782-xStamp it…

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A shock to the system

Posted on Mar 24th, 2021 - By Grant Miura

Nature Chemical Biology, Published online: 24 March 2021; doi:10.1038/s41589-021-00781-yA shock to the…

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Water-processable, biodegradable and coatable aquaplastic from engineered biofilms

Posted on Mar 18th, 2021 - By Anna M. Duraj-Thatte

Nature Chemical Biology, Published online: 18 March 2021; doi:10.1038/s41589-021-00773-yBuilt of bacterial biofilm proteins, aquaplastic is a biodegradable material that can easily be processed from a hydrogel state into bulk materials, is resistant to acids, bases and organic solvents, and is easily healable and weldable in…

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Peroxisomal-derived ether phospholipids link nucleotides to respirasome assembly

Posted on Mar 15th, 2021 - By Christopher F. Bennett

Nature Chemical Biology, Published online: 15 March 2021; doi:10.1038/s41589-021-00772-zA chemical screen identifies DHODH inhibitors as robust activators of mitochondrial respirasome assembly. Lipidomics reveal that peroxisomal-derived ether phospholipids accumulate in mitochondria during nucleotide deprivation to drive…

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YAP-dependent proliferation by a small molecule targeting annexin A2

Posted on Mar 15th, 2021 - By Sophia Z. Shalhout

Nature Chemical Biology, Published online: 15 March 2021; doi:10.1038/s41589-021-00755-0Annexin A2 (ANXA2) is identified as the target of a pharmacological YAP activator and as a druggable component of the Hippo…

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ANXious for YAP

Posted on Mar 15th, 2021 - By Toshiro Moroishi

Nature Chemical Biology, Published online: 15 March 2021; doi:10.1038/s41589-021-00766-xYAP is a major downstream effector of the Hippo intracellular signaling pathway, with key roles in organ development, regeneration, and cancer biology. A small molecule that targets Annexin (ANX) acts through YAP to promote rapid epidermal tissue…

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Deform the membrane, cAPTure the lipid

Posted on Mar 11th, 2021 - By Jennifer Greaves

Nature Chemical Biology, Published online: 11 March 2021; doi:10.1038/s41589-021-00754-1Acyl protein thioesterases are critical regulators of S-acylation, removing acyl chains from dynamically S-acylated proteins. A cytosolic deacylase, APT2, is S-acylated by zDHHC3 and zDHHC7 and is predicted to deform the lipid bilayer to extract acyl chains, capturing them within a hydrophobic…

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Functional elucidation of TfuA in peptide backbone thioamidation

Posted on Mar 11th, 2021 - By Andi Liu

Nature Chemical Biology, Published online: 11 March 2021; doi:10.1038/s41589-021-00771-0TfuA, YcaO and thiol donor protein, ThiS, collaborate in peptide backbone thioamidation of McrA and during the biosynthesis of certain ribosomally synthesized and post-translationally modified peptide (RiPP) natural…

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Palmitoylated acyl protein thioesterase APT2 deforms membranes to extract substrate acyl chains

Posted on Mar 11th, 2021 - By Laurence Abrami

Nature Chemical Biology, Published online: 11 March 2021; doi:10.1038/s41589-021-00753-2Acyl protein thioesterase APT2 interacts with membranes via its charged β-tongue, becomes palmitoylated by ZDHHC3/7 and deforms the bilayer to extract substrate acyl chains. APT2 deacylation leads to its membrane release and…

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Redox-coupled rhythm and brews

Posted on Mar 8th, 2021 - By John S. O’Neill

Nature Chemical Biology, Published online: 08 March 2021; doi:10.1038/s41589-021-00777-8A genetically encoded real-time redox reporter reveals that H2O2-signaling peroxiredoxin (PRX) proteins couple yeast metabolic oscillations with the cell division cycle. This new PRX function suggests fresh avenues for exploring circadian regulation of cell division and…

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STACKing the odds for discoveries

Posted on Mar 8th, 2021 - By Mariluz Soula

Nature Chemical Biology, Published online: 08 March 2021; doi:10.1038/s41589-021-00743-4Characterization of cell death kinetics identifies new on- and off-target small-molecule modulators of ferroptosis and reveals a role of amino acid metabolism in regulating ferroptosis…

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Mutanofactin promotes adhesion and biofilm formation of cariogenic <i>Streptococcus mutans</i>

Posted on Mar 4th, 2021 - By Zhong-Rui Li

Nature Chemical Biology, Published online: 04 March 2021; doi:10.1038/s41589-021-00745-2The mutanofactin family of lipopeptide natural products, produced by strains of cariogenic Streptococcus mutans, promotes biofilm formation via increased cell-surface hydrophobicity and binding to extracellular…

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Discovery of a first-in-class CDK2 selective degrader for AML differentiation therapy

Posted on Mar 4th, 2021 - By Liguo Wang

Nature Chemical Biology, Published online: 04 March 2021; doi:10.1038/s41589-021-00742-5A selective and potent CDK2 degrader was developed that induced differentiation of acute myeloid leukemia cell lines and primary patient…

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Author Correction: Cytochrome P450 oxidoreductase contributes to phospholipid peroxidation in ferroptosis

Posted on Mar 2nd, 2021 - By Yilong Zou

Nature Chemical Biology, Published online: 02 March 2021; doi:10.1038/s41589-021-00767-wAuthor Correction: Cytochrome P450 oxidoreductase contributes to phospholipid peroxidation in…

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Orphan receptor GPR37L1 remains unliganded

Posted on Mar 1st, 2021 - By Tony Ngo

Nature Chemical Biology, Published online: 01 March 2021; doi:10.1038/s41589-021-00748-zOrphan receptor GPR37L1 remains…

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Binding site for activator MDL-801 on SIRT6

Posted on Mar 1st, 2021 - By Weijie You

Nature Chemical Biology, Published online: 01 March 2021; doi:10.1038/s41589-021-00749-yBinding site for activator MDL-801 on…

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Reply to: Binding site for MDL-801 on SIRT6

Posted on Mar 1st, 2021 - By Zhimin Huang

Nature Chemical Biology, Published online: 01 March 2021; doi:10.1038/s41589-021-00750-5Reply to: Binding site for MDL-801 on…

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Oncohistones: corruption at the core

Posted on Mar 1st, 2021 - By Kanishk Jain

Nature Chemical Biology, Published online: 01 March 2021; doi:10.1038/s41589-021-00764-zHigh-throughput biochemical and biological analyses of disease-associated histone mutations reveal key residues in globular cores that affect chromatin remodeling, nucleosome stability, and stem cell…

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Retraction Note: Orphan receptor ligand discovery by pickpocketing pharmacological neighbors

Posted on Mar 1st, 2021 - By Tony Ngo

Nature Chemical Biology, Published online: 01 March 2021; doi:10.1038/s41589-021-00746-1Retraction Note: Orphan receptor ligand discovery by pickpocketing pharmacological…

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ROS regulated reversible protein phase separation synchronizes plant flowering

Posted on Feb 25th, 2021 - By Xiaozhen Huang

Nature Chemical Biology, Published online: 25 February 2021; doi:10.1038/s41589-021-00739-0Plants utilize naturally produced ROS in shoot apical stem cells as a developmental signal to trigger phase separation of TMF. The resulting transcriptional condensates repress expression of the floral identity gene to precisely time…

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Redox control of flowering

Posted on Feb 25th, 2021 - By Christine H. Foyer

Nature Chemical Biology, Published online: 25 February 2021; doi:10.1038/s41589-021-00758-xUsing an interdisciplinary approach, hydrogen-peroxide-induced phase separation in the intrinsically disordered regions of the TERMINATING FLOWER transcription factor proteins was shown to regulate the shoot apical meristem through repression of the floral identity gene called…

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Specialized self-protection

Posted on Feb 23rd, 2021 - By Caitlin Deane

Nature Chemical Biology, Published online: 23 February 2021; doi:10.1038/s41589-021-00759-wSpecialized…

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Disrupting the phase balance

Posted on Feb 23rd, 2021 - By Grant Miura

Nature Chemical Biology, Published online: 23 February 2021; doi:10.1038/s41589-021-00760-3Disrupting the phase…

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Modified signals

Posted on Feb 23rd, 2021 - By Yiyun Song

Nature Chemical Biology, Published online: 23 February 2021; doi:10.1038/s41589-021-00762-1Modified…

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Orchestration by inositol phosphates

Posted on Feb 23rd, 2021 - By Mirella Bucci

Nature Chemical Biology, Published online: 23 February 2021; doi:10.1038/s41589-021-00761-2Orchestration by inositol…

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Optical control of fast and processive engineered myosins in vitro and in living cells

Posted on Feb 18th, 2021 - By Paul V. Ruijgrok

Nature Chemical Biology, Published online: 18 February 2021; doi:10.1038/s41589-021-00740-7High-performance engineered myosins robustly change speed or direction in response to an optical signal. In living cells, these motors localize to the tips of protrusions when illuminated and deliver molecular…

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A community resource for paired genomic and metabolomic data mining

Posted on Feb 15th, 2021 - By Michelle A. Schorn

Nature Chemical Biology, Published online: 15 February 2021; doi:10.1038/s41589-020-00724-zGenomics and metabolomics are widely used to explore specialized metabolite diversity. The Paired Omics Data Platform is a community initiative to systematically document links between metabolome and (meta)genome data, aiding identification of natural product biosynthetic origins and metabolite…

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Peroxiredoxins couple metabolism and cell division in an ultradian cycle

Posted on Feb 11th, 2021 - By Prince Saforo Amponsah

Nature Chemical Biology, Published online: 11 February 2021; doi:10.1038/s41589-020-00728-9Hydrogen peroxide and peroxiredoxin oxidation levels oscillate during the yeast metabolic cycle, while the absence of peroxiredoxins or the use of thiol oxidants and reductants disrupts metabolic cycling and its coupling with cell…

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