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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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Structure- and mechanism-guided design of single fluorescent protein-based biosensors

Posted on Feb 8th, 2021 - By Yusuke Nasu

Nature Chemical Biology, Published online: 08 February 2021; doi:10.1038/s41589-020-00718-xUsing extensive knowledge about the structures and mechanisms of genetically encoded fluorescent biosensors, this Perspective provides guidelines to aid and accelerate the development of an increasingly broad range of high-performance imaging…

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Synthetic protein quality control to enhance full-length translation in bacteria

Posted on Feb 4th, 2021 - By Jina Yang

Nature Chemical Biology, Published online: 04 February 2021; doi:10.1038/s41589-021-00736-3A synthetic protein quality control system (ProQC) uses RNA hybridization to enhance translation of full-length proteins in coupled transcription–translation systems to optimize production of biosynthetic enzymes for metabolic engineering…

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Author Correction: A cytochrome <i>c</i> is the natural electron acceptor for nicotine oxidoreductase

Posted on Feb 4th, 2021 - By Mark Dulchavsky

Nature Chemical Biology, Published online: 04 February 2021; doi:10.1038/s41589-021-00756-zAuthor Correction: A cytochrome c is the natural electron acceptor for nicotine…

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Phospholipase iPLA<sub>2</sub>β averts ferroptosis by eliminating a redox lipid death signal

Posted on Feb 4th, 2021 - By Wan-Yang Sun

Nature Chemical Biology, Published online: 04 February 2021; doi:10.1038/s41589-020-00734-xCa2+-independent phospholipase A2β cleaves an oxidized form of phosphatidylethanolamine (PE) involved in ferroptosis such that increases in PE sensitize cells to ferroptosis. A mutant allele of the enzyme links neurodegeneration and…

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Yeast- and antibody-based tools for studying tryptophan C-mannosylation

Posted on Feb 4th, 2021 - By Alan John

Nature Chemical Biology, Published online: 04 February 2021; doi:10.1038/s41589-020-00727-wAn engineered Pichia pastoris strain enables the synthesis of tryptophan C-mannosylated proteins, and selected monoclonal antibodies provide tools for detecting these modified proteins and studying their…

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Allostery governs Cdk2 activation and differential recognition of CDK inhibitors

Posted on Feb 1st, 2021 - By Abir Majumdar

Nature Chemical Biology, Published online: 01 February 2021; doi:10.1038/s41589-020-00725-yDissection of the allosteric coupling in the cyclin-dependent kinase Cdk2 shows that this allostery explains how the kinase is activated by cyclin binding and phosphorylation and how it differentiates between Cdk2 and Cdk4…

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Computation-guided optimization of split protein systems

Posted on Feb 1st, 2021 - By Taylor B. Dolberg

Nature Chemical Biology, Published online: 01 February 2021; doi:10.1038/s41589-020-00729-8A computational design strategy guided by biophysical principles enables engineering of split protein systems to tune their degree of interfacial destabilization, and thus reconstitution propensity, while preserving stability and catalytic…

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Author Correction: Optical control of L-type Ca<sup>2+</sup> channels using a diltiazem photoswitch

Posted on Jan 29th, 2021 - By Timm Fehrentz

Nature Chemical Biology, Published online: 29 January 2021; doi:10.1038/s41589-021-00744-3Author Correction: Optical control of L-type Ca2+ channels using a diltiazem…

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Chemical systems biology reveals mechanisms of glucocorticoid receptor signaling

Posted on Jan 28th, 2021 - By Nelson E. Bruno

Nature Chemical Biology, Published online: 28 January 2021; doi:10.1038/s41589-020-00719-wA systems-based approach to profile glucocorticoid (GC) receptor ligands in a broad range of assays representing different phenotypic responses linked these to transcriptional profiles and led to separation of GC therapeutic effects from side…

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One-step data storage in cellular DNA

Posted on Jan 26th, 2021 - By Santi Bhattarai-Kline

Nature Chemical Biology, Published online: 26 January 2021; doi:10.1038/s41589-021-00737-2The cumbersome encoding of digital data to cellular DNA hinders the use of cells as living hard drives. A new approach transfers digital information directly into cellular DNA by converting electrical signals into stable and interpretable changes in the genomes of bacterial…

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A Fbxo48 inhibitor prevents pAMPKα degradation and ameliorates insulin resistance

Posted on Jan 25th, 2021 - By Yuan Liu

Nature Chemical Biology, Published online: 25 January 2021; doi:10.1038/s41589-020-00723-0E3 ligase subunit protein Fbxo48 interacts with phosphorylated Ampkα and mediates its proteasomal degradation. Interruption of the pAmpkα/Fbxo48 interaction by a small-molecule BC1618 promoted Ampkα activation and improved insulin…

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Chemical detection triggers honey bee defense against a destructive parasitic threat

Posted on Jan 25th, 2021 - By Fanny Mondet

Nature Chemical Biology, Published online: 25 January 2021; doi:10.1038/s41589-020-00720-3In honey bee colonies infested with the mite Varroa destructor, six Varroa-parasitization-specific (VPS) compounds trigger protective behavior in the bees, which are able to distinguish VPS compounds from healthy signals and recognize an infested…

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The case of the missing allosteric ribozymes

Posted on Jan 25th, 2021 - By Shanker S. S. Panchapakesan

Nature Chemical Biology, Published online: 25 January 2021; doi:10.1038/s41589-020-00713-2This Perspective summarizes the known types of ligand-controlled ribozymes and riboswitches and discusses the reasons why allosteric ribozymes formed by fusion of RNA enzymes and RNA aptamers are rare in today’s biological…

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Cryo-EM structure of the RNA-guided ribonuclease Cas12g

Posted on Jan 25th, 2021 - By Zhuang Li

Nature Chemical Biology, Published online: 25 January 2021; doi:10.1038/s41589-020-00721-2The cryo-EM structures of Cas12g in complex with sgRNA in the absence and presence of target RNA reveal that the duplex formed by target RNA and crRNA binds to a central channel of Cas12g, inducing its conformational change and…

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Addendum: MCC950 closes the active conformation of NLRP3 to an inactive state

Posted on Jan 25th, 2021 - By Ana Tapia-Abellán

Nature Chemical Biology, Published online: 25 January 2021; doi:10.1038/s41589-021-00741-6Addendum: MCC950 closes the active conformation of NLRP3 to an inactive…

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The enemy of my enemy

Posted on Jan 22nd, 2021 - By Caitlin Deane

Nature Chemical Biology, Published online: 22 January 2021; doi:10.1038/s41589-020-00731-0The enemy of my…

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Flowery endocytosis

Posted on Jan 22nd, 2021 - By Mirella Bucci

Nature Chemical Biology, Published online: 22 January 2021; doi:10.1038/s41589-020-00733-yFlowery…

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Publisher Correction: Rational discovery of molecular glue degraders via scalable chemical profiling

Posted on Jan 15th, 2021 - By Cristina Mayor-Ruiz

Nature Chemical Biology, Published online: 15 January 2021; doi:10.1038/s41589-021-00735-4Publisher Correction: Rational discovery of molecular glue degraders via scalable chemical…

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Robust direct digital-to-biological data storage in living cells

Posted on Jan 11th, 2021 - By Sung Sun Yim

Nature Chemical Biology, Published online: 11 January 2021; doi:10.1038/s41589-020-00711-4A new DNA data storage technology—data recording in vivo by electrical stimulation (DRIVES)—places CRISPR-based DNA encoding activity under electrochemical control by coupling cellular redox state to CRISPR array gene…

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Laboratory evolution of a sortase enzyme that modifies amyloid-β protein

Posted on Jan 11th, 2021 - By Christopher J. Podracky

Nature Chemical Biology, Published online: 11 January 2021; doi:10.1038/s41589-020-00706-1Laboratory evolution of the bacterial transpeptidase sortase A coupled with yeast display selection enables a change of the enzyme’s substrate preference to recognize and covalently label endogenous amyloid-β protein, impeding the protein’s ability to…

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Hierarchical chemical determination of amyloid polymorphs in neurodegenerative disease

Posted on Jan 11th, 2021 - By Dan Li

Nature Chemical Biology, Published online: 11 January 2021; doi:10.1038/s41589-020-00708-zThis Perspective summarizes the recent advances in the structural diversity of amyloid fibrils and discusses the roles of post-translational modifications and chemical cofactors in the conformational determination of fibril…

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A cytochrome <i>c</i> is the natural electron acceptor for nicotine oxidoreductase

Posted on Jan 11th, 2021 - By Mark Dulchavsky

Nature Chemical Biology, Published online: 11 January 2021; doi:10.1038/s41589-020-00712-3Unlike other amine oxidase-family enzymes, nicotine oxidoreductase (NicA2) reacts very slowly with oxygen, prompting the search for and identification of a cytochrome c protein (CycN) that is responsible for accepting electrons from NicA2 in…

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Harnessing nanotechnology to expand the toolbox of chemical biology

Posted on Jan 7th, 2021 - By Ryan M. Williams

Nature Chemical Biology, Published online: 07 January 2021; doi:10.1038/s41589-020-00690-6This Perspective introduces chemical biologists to potentially useful nanotechnologies, aims to inspire nanotechnologists to address questions relevant to chemical biology, and identifies possible opportunities for the two fields to…

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Molecular basis for arginine C-terminal degron recognition by Cul2<sup>FEM1</sup> E3 ligase

Posted on Jan 4th, 2021 - By Xinyan Chen

Nature Chemical Biology, Published online: 04 January 2021; doi:10.1038/s41589-020-00704-3Structural characterization of the substrate adapters of the C-degron pathway reveals the selective recognition mode towards substrates with C-terminal arginine by FEM1A/C and…

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Bottom-up de novo design of functional proteins with complex structural features

Posted on Jan 4th, 2021 - By Che Yang

Nature Chemical Biology, Published online: 04 January 2021; doi:10.1038/s41589-020-00699-xBeginning with a functional site and building a supporting scaffold around it enables the de novo design of proteins with distinct binding motifs for use in biosensors to detect antibody responses and as ligands of synthetic signaling…

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Molecular basis for ubiquitin ligase CRL2<sup>FEM1C</sup>-mediated recognition of C-degron

Posted on Jan 4th, 2021 - By Xiaojie Yan

Nature Chemical Biology, Published online: 04 January 2021; doi:10.1038/s41589-020-00703-4Crystal structures of FEM1C in apo and in complex with a C-degron ending with arginine reveal a binding pocket in FEM1C that recognizes C-degrons and the essential role of C-terminal arginine for…

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Conformational rearrangement during activation of a metabotropic glutamate receptor

Posted on Jan 4th, 2021 - By Brandon Wey-Hung Liauw

Nature Chemical Biology, Published online: 04 January 2021; doi:10.1038/s41589-020-00702-5Single-molecule FRET of mGluR2 shows that the conformations of the ligand-binding domain and the linked cysteine-rich domain are loosely coupled during ligand-induced activation and defines two pre-active states linking inactive and active…

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Living materials fabricated via gradient mineralization of light-inducible biofilms

Posted on Dec 21st, 2020 - By Yanyi Wang

Nature Chemical Biology, Published online: 21 December 2020; doi:10.1038/s41589-020-00697-zCoupling light-inducible bacterial biofilm formation with hydroxyapatite mineralization enables the synthesis of living patterned and gradient composite biomaterials with control over the degree of mineralization and the ability to…

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Author Correction: Ion channels as lipid sensors: from structures to mechanisms

Posted on Dec 17th, 2020 - By Mackenzie J. Thompson

Nature Chemical Biology, Published online: 17 December 2020; doi:10.1038/s41589-020-00722-1Author Correction: Ion channels as lipid sensors: from structures to…

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Controlling and enhancing CRISPR systems

Posted on Dec 16th, 2020 - By Haridha Shivram

Nature Chemical Biology, Published online: 16 December 2020; doi:10.1038/s41589-020-00700-7This Review summarizes recent advances in CRISPR–Cas regulation mechanisms by natural biomolecules that enhance or inhibit CRIPSR–Cas immunity, as well as their applications in CRISPR biology and…

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Voices of chemical biology

Nature Chemical Biology, Published online: 16 December 2020; doi:10.1038/s41589-020-00714-1We asked a collection of chemical biologists, “What is the most exciting frontier area in chemical biology and what key technology is needed to advance knowledge and applications in this area?” and reveal some of the perspectives we…

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Linkage-specific ubiquitin chain formation depends on a lysine hydrocarbon ruler

Posted on Dec 7th, 2020 - By Joanna Liwocha

Nature Chemical Biology, Published online: 07 December 2020; doi:10.1038/s41589-020-00696-0Using synthetic ubiquitins with non-natural acceptor site, the authors revealed that the length of lysine side chain in acceptor ubiquitins affects ubiquitin chain linkage specificity with native lysine as the preferred…

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Cryptic phosphorylation in nucleoside natural product biosynthesis

Posted on Nov 30th, 2020 - By Matthew M. Draelos

Nature Chemical Biology, Published online: 30 November 2020; doi:10.1038/s41589-020-00656-8Rather than their expected role in self-immunity, kinases encoded in the biosynthetic gene clusters of nucleoside natural products catalyze the phosphorylation of an early intermediate, a modification that is later removed in a downstream…

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Cell type-selective secretome profiling in vivo

Posted on Nov 16th, 2020 - By Wei Wei

Nature Chemical Biology, Published online: 16 November 2020; doi:10.1038/s41589-020-00698-yA proximity labeling strategy enables enrichment of cell type-selective secretomes in mice by direct biochemical purification of biotinylated polypeptides from blood…

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Defining new chemical space for drug penetration into Gram-negative bacteria

Posted on Nov 16th, 2020 - By Shibin Zhao

Nature Chemical Biology, Published online: 16 November 2020; doi:10.1038/s41589-020-00674-6The difficulty of antibiotic discovery posed by the double-membrane cell envelope of Gram-negative bacteria and active drug efflux requires better understanding of bacterial permeability and compound accumulation, and more diverse chemical…

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Snapshots and ensembles of BTK and cIAP1 protein degrader ternary complexes

Posted on Nov 16th, 2020 - By James Schiemer

Nature Chemical Biology, Published online: 16 November 2020; doi:10.1038/s41589-020-00686-2The authors report PROTAC ternary complex structures involving the E3 ligase cIAP1 and target protein BTK, showing that cooperativity is not always correlated with degradation…

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The conformational cycle of a prototypical voltage-gated sodium channel

Posted on Nov 16th, 2020 - By William A. Catterall

Nature Chemical Biology, Published online: 16 November 2020; doi:10.1038/s41589-020-0644-4The conformational cycle of a bacterial voltage-gated sodium channel as it transitions from resting to activated open to inactivated closed states can be constructed from various crystal structure…

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Delimiting lipids

Nature Chemical Biology, Published online: 16 November 2020; doi:10.1038/s41589-020-00701-6This themed issue features a collection of articles that explore long-standing questions in the study of lipids and…

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Making use of surplus sugar

Posted on Nov 16th, 2020 - By Niels Agerbirk

Nature Chemical Biology, Published online: 16 November 2020; doi:10.1038/s41589-020-00687-1Insects have many ways of disabling plant chemical defenses during feeding. Plant phloem feeders use surplus ingested sugar to block the activation of glucosinolate toxins, providing a target for precise resistance…

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Chemically informed analyses of metabolomics mass spectrometry data with Qemistree

Posted on Nov 16th, 2020 - By Anupriya Tripathi

Nature Chemical Biology, Published online: 16 November 2020; doi:10.1038/s41589-020-00677-3Qemistree uses fragmentation spectra to predict molecular fingerprints and represent their relationships as a tree, enabling comparison of metabolomics data across different experimental conditions and exploration of chemical diversity in…

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Ion channels as lipid sensors: from structures to mechanisms

Posted on Nov 16th, 2020 - By Mackenzie J. Thompson

Nature Chemical Biology, Published online: 16 November 2020; doi:10.1038/s41589-020-00693-3Ion channel structures reveal mechanisms of lipid action, including how channel gating is altered by direct binding of signaling lipids and those within the membrane itself, as well as mechanical and architectural effects of membrane…

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Chemical reversal of abnormalities in cells carrying mitochondrial DNA mutations

Posted on Nov 9th, 2020 - By Hiroki Kobayashi

Nature Chemical Biology, Published online: 09 November 2020; doi:10.1038/s41589-020-00676-4Tryptolinamide (TLAM) is a small molecule compound that inhibits phosphofructokinase-1 activity and rescues the metabolic defects of patient-derived induced pluripotent stem cell lines with mutated mitochondrial…

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Production of Tyrian purple indigoid dye from tryptophan in <i>Escherichia coli</i>

Posted on Nov 2nd, 2020 - By Jeongchan Lee

Nature Chemical Biology, Published online: 02 November 2020; doi:10.1038/s41589-020-00684-4A two-cell setup containing tryptophanase, a flavin-dependent monooxygenase and a regiospecific halogenase (linked to a flavin reductase as a solubility tag) enables the production of 6,6'-dibromoindigo and other indigoid dyes in Escherichia…

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Synthetic yeast brews neuroactive compounds

Posted on Oct 28th, 2020 - By Yang Gu

Nature Chemical Biology, Published online: 28 October 2020; doi:10.1038/s41589-020-00691-5Metabolic engineering offers the flexibility to meet market demand for bioactive natural products but can be hampered when a necessary protein or intermediate is toxic. In yeast, modifying the subcellular localization of biosynthetic enzymes can alleviate toxicity and increase production…

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Structural basis for persulfide-sensing specificity in a transcriptional regulator

Posted on Oct 26th, 2020 - By Daiana A. Capdevila

Nature Chemical Biology, Published online: 26 October 2020; doi:10.1038/s41589-020-00671-9Structural and kinetic analyses of the transcriptional repressor SqrR in multiple states indicate that its persulfide selectivity is determined by structural frustration in the disulfide form, favoring formation of the tetrasulfide-bridged…

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Rerouting plant terpene biosynthesis enables momilactone pathway elucidation

Posted on Oct 26th, 2020 - By Ricardo De La Peña

Nature Chemical Biology, Published online: 26 October 2020; doi:10.1038/s41589-020-00669-3Redirecting plant diterpene biosynthesis from the chloroplast to the cytosolic, high-flux mevalonate pathway increases intermediate and product titers to support the elucidation and reconstitution of momilactone…

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Interhelical interactions within the STIM1 CC1 domain modulate CRAC channel activation

Posted on Oct 26th, 2020 - By Petr Rathner

Nature Chemical Biology, Published online: 26 October 2020; doi:10.1038/s41589-020-00672-8The helical bundle structure of the CC1 domain of STIM1 of the store-activated calcium channel CRAC is crucial to maintaining the channel resting state, and helix–helix interactions can be manipulated to normalize a disease-linked STIM1…

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Visualizing a protonated RNA state that modulates microRNA-21 maturation

Posted on Oct 26th, 2020 - By Jared T. Baisden

Nature Chemical Biology, Published online: 26 October 2020; doi:10.1038/s41589-020-00667-5The authors identified a pH-dependent protonated status in the miR-21 precursor, which leads to additional base pairing in its secondary structure, thus affecting Dicer processing and miR-21…

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SARS-CoV-2 M<sup>pro</sup> inhibitors and activity-based probes for patient-sample imaging

Posted on Oct 22nd, 2020 - By Wioletta Rut

Nature Chemical Biology, Published online: 22 October 2020; doi:10.1038/s41589-020-00689-zScreening for substrate preference of the SARS-CoV and SARS-CoV-2 main protease Mpro leads to the development of activity-based probes useful for structural analysis and for visualization of active Mpro in infected patient epithelial…

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Bi-paratopic and multivalent VH domains block ACE2 binding and neutralize SARS-CoV-2

Posted on Oct 20th, 2020 - By Colton J. Bracken

Nature Chemical Biology, Published online: 20 October 2020; doi:10.1038/s41589-020-00679-1A screening approach finds VH-domain antibodies that bind the SARS-CoV-2 Spike protein receptor-binding domain at its interface with host ACE2. Bi-paratopic and multivalent binders have high affinity and…

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Cuticle thickness affects dynamics of volatile emission from petunia flowers

Posted on Oct 19th, 2020 - By Pan Liao

Nature Chemical Biology, Published online: 19 October 2020; doi:10.1038/s41589-020-00670-wThe plant cuticle was initially thought to act as a passive diffusion barrier. Genetic and metabolic analysis reveals that it is also a sink/concentrator for volatiles protecting cells from toxic effects of these hydrophobic…

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Launching the missile

Posted on Oct 16th, 2020 - By Yiyun Song

Nature Chemical Biology, Published online: 16 October 2020; doi:10.1038/s41589-020-00683-5Launching the…

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It’s a trap!

Posted on Oct 16th, 2020 - By Caitlin Deane

Nature Chemical Biology, Published online: 16 October 2020; doi:10.1038/s41589-020-00680-8It’s a…

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Advanced rules of relays

Posted on Oct 16th, 2020 - By Sonja Lorenz

Nature Chemical Biology, Published online: 16 October 2020; doi:10.1038/s41589-020-0632-8Transfer of ubiquitin onto target proteins requires controlled interplay between E2 conjugating enzymes and E3 ligases. The structure of a trapped E2~Ub/RCR E3 transfer intermediate provides novel insight into the diversity of mechanisms used to fine tune this…

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