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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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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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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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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p63 is a cereblon substrate involved in thalidomide teratogenicity

Posted on Oct 7th, 2019 - By Tomoko Asatsuma-Okumura

Nature Chemical Biology, Published online: 07 October 2019; doi:10.1038/s41589-019-0366-7Zebrafish p63 isoforms were identified as thalidomide-dependent neosubstrates of the cereblon-containing E3 ligase complex. ∆Np63α and TAp63α are responsible for thalidomide-induced malformations of pectoral fins and otic vesicles,…

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Mapping spatial transcriptome with light-activated proximity-dependent RNA labeling

Posted on Oct 7th, 2019 - By Pengchong Wang

Nature Chemical Biology, Published online: 07 October 2019; doi:10.1038/s41589-019-0368-5A light-activated RNA labeling method was developed to determine spatial organization of a transcriptome and found that ribosomal proteins and oxidative phosphorylation pathway proteins are highly enriched at the outer mitochondrial…

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Axonal iron transport in the brain modulates anxiety-related behaviors

Posted on Oct 7th, 2019 - By Zhuo Wang

Nature Chemical Biology, Published online: 07 October 2019; doi:10.1038/s41589-019-0371-xIron is transported from the ventral hippocampus to the medial prefrontal cortex unidirectionally in the brain via axonal projections. This transport is involved in mediating anxiety and the anxiolytic effects of…

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A small molecule interacts with VDAC2 to block mouse BAK-driven apoptosis

Posted on Oct 7th, 2019 - By Mark F. van Delft

Nature Chemical Biology, Published online: 07 October 2019; doi:10.1038/s41589-019-0365-8A phenotypic screen led to the identification of potent inhibitors of mouse BAK-driven apoptosis. The compounds interact with VDAC2 and stabilize its interaction with BAK, blocking apoptosis at an early stage to preserve long-term cell…

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A lipid site shapes the agonist response of a pentameric ligand-gated ion channel

Posted on Oct 7th, 2019 - By Camille M. Hénault

Nature Chemical Biology, Published online: 07 October 2019; doi:10.1038/s41589-019-0369-4A crystal structure of prokaryotic pentameric ligand-gated ion channel ELIC reveals a lipid-binding site at the interface between subunits that is shaped by a flexible helix important for channel desensitization upon lipid…

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The morphogen Sonic hedgehog inhibits its receptor Patched by a pincer grasp mechanism

Posted on Sep 23rd, 2019 - By Amalie F. Rudolf

Nature Chemical Biology, Published online: 23 September 2019; doi:10.1038/s41589-019-0370-yCholesterol can function as both a substrate and an inhibitor of the Hedgehog receptor Patched. Structural analysis and molecular dynamics simulations reveal that cholesterol inhibits Patched by inserting into its extracellular…

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Near-equilibrium glycolysis supports metabolic homeostasis and energy yield

Posted on Sep 23rd, 2019 - By Junyoung O. Park

Nature Chemical Biology, Published online: 23 September 2019; doi:10.1038/s41589-019-0364-9A 2H and 13C tracing strategy was used for efficient determination of glycolytic thermodynamics, revealing near-equilibrium glycolytic steps enabling rapid flux adaptation and, in Clostridium cellulolyticum, enhanced ATP…

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A family of radical halogenases for the engineering of amino-acid-based products

Posted on Sep 23rd, 2019 - By Monica E. Neugebauer

Nature Chemical Biology, Published online: 23 September 2019; doi:10.1038/s41589-019-0355-xStructural characterization of the amino-acid-modifying radical halogenase BesD and identification of new members of this protein family provides insight into the enzymatic mechanism and enables biocatalytic production of halogenated amino…

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Colibactin comes to light

Posted on Sep 20th, 2019 - By Caitlin Deane

Nature Chemical Biology, Published online: 20 September 2019; doi:10.1038/s41589-019-0373-8Colibactin comes to…

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First contact

Posted on Sep 20th, 2019 - By Yiyun Song

Nature Chemical Biology, Published online: 20 September 2019; doi:10.1038/s41589-019-0375-6First…

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A NAMe-tag for ALS

Posted on Sep 20th, 2019 - By Mirella Bucci

Nature Chemical Biology, Published online: 20 September 2019; doi:10.1038/s41589-019-0374-7A NAMe-tag for…

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The root of the cause

Posted on Sep 20th, 2019 - By Grant Miura

Nature Chemical Biology, Published online: 20 September 2019; doi:10.1038/s41589-019-0376-5The root of the…

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Development of targeted protein degradation therapeutics

Posted on Sep 16th, 2019 - By Philip P. Chamberlain

Nature Chemical Biology, Published online: 16 September 2019; doi:10.1038/s41589-019-0362-yThis Perspective summarizes recent discoveries that have laid the foundation for targeted degradation therapeutics and discusses the current state of understanding and consideration involved in developing these protein…

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DNA repair complex licenses acetylation of H2A.Z.1 by KAT2A during transcription

Posted on Sep 16th, 2019 - By M. Semer

Nature Chemical Biology, Published online: 16 September 2019; doi:10.1038/s41589-019-0354-yKAT2A acetylates histone variant H2A.Z to regulate transactivation of XPC and RAR positively regulated genes. The DNA repair complex XPC–RAD23–CEN2 interacts with H2A.Z and KAT2A to license the latter’s histone acetyltransferase…

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Versatile biomanufacturing through stimulus-responsive cell–material feedback

Posted on Sep 16th, 2019 - By Zhuojun Dai

Nature Chemical Biology, Published online: 16 September 2019; doi:10.1038/s41589-019-0357-8Encapsulation of engineered bacteria in environmentally responsive materials enables on-demand protein production coupled to downstream processes such as protein purification, on-chip enzyme kinetics and metabolic production of fatty…

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Cargo adaptors regulate stepping and force generation of mammalian dynein–dynactin

Posted on Sep 9th, 2019 - By Mohamed M. Elshenawy

Nature Chemical Biology, Published online: 09 September 2019; doi:10.1038/s41589-019-0352-0Single-molecule analysis revealed that the velocity and force generation of the mammalian dynein–dynactin complex is regulated by activating adaptors and tail–tail interactions between two…

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The tail wags the motor

Posted on Sep 9th, 2019 - By Richard J. McKenney

Nature Chemical Biology, Published online: 09 September 2019; doi:10.1038/s41589-019-0367-6Cytoplasmic dynein is a complex molecular motor that steps along microtubules. Advanced biophysical measurements reveal a surprising role for the dynein tail domain in the allosteric control of dynein’s mechanochemistry within assemblies composed of multiple dynein…

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Dynamic membrane topology in an unassembled membrane protein

Posted on Sep 9th, 2019 - By Maximilian Seurig

Nature Chemical Biology, Published online: 09 September 2019; doi:10.1038/s41589-019-0356-9The topology of homodimeric membrane protein EmrE is dynamic and includes unassisted flipping of an N-terminal helix in and out of the membrane long after co-translational insertion. Dimerization locks the helix to limit topological…

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mRNA structure determines modification by pseudouridine synthase 1

Posted on Sep 2nd, 2019 - By Thomas M. Carlile

Nature Chemical Biology, Published online: 02 September 2019; doi:10.1038/s41589-019-0353-zAn in vitro method was developed to screen mRNA sites for psedouridine modification by specific pseudouridylating enzymes and identify an RNA structural motif for Pus1, which can be used to predict new pseudouridylated mRNA targets in…

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A blue light receptor that mediates RNA binding and translational regulation

Posted on Aug 26th, 2019 - By Anna M. Weber

Nature Chemical Biology, Published online: 26 August 2019; doi:10.1038/s41589-019-0346-yA light-oxygen-voltage photoreceptor was found to bind short RNA stem loops in a light-dependent manner, which can be harnessed to regulate gene expression in bacteria and mammalian…

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Fosmidomycin biosynthesis diverges from related phosphonate natural products

Posted on Aug 26th, 2019 - By Elizabeth I. Parkinson

Nature Chemical Biology, Published online: 26 August 2019; doi:10.1038/s41589-019-0343-1The biosynthetic pathway for the phosphonate natural product dehydrofosmidomycin differs from that of the related compound FR-900098, involving rearrangement of a two-carbon phosphonate precursor catalyzed by a 2-oxoglutarate-dependent…

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Extracellular phosphorylation drives the formation of neuronal circuitry

Posted on Aug 26th, 2019 - By Hidekiyo Harada

Nature Chemical Biology, Published online: 26 August 2019; doi:10.1038/s41589-019-0345-zVia its receptor LRP5, Wnt3a stimulates axonal growth in retinal ganglion neurons. Phosphorylation of co-receptor RGMb by VLK induces LRP5 internalization to limit Wnt3a signaling and reduce axon…

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CRISPR-Cas9 screens identify regulators of antibody–drug conjugate toxicity

Posted on Aug 26th, 2019 - By C. Kimberly Tsui

Nature Chemical Biology, Published online: 26 August 2019; doi:10.1038/s41589-019-0342-2A series of genome-wide and targeted CRISPR screens uncovered regulators of antibody–drug conjugate (ADC) toxicity. Depletion of sialic acids was found to enhance ADC lysosomal delivery, in part by reducing ADC…

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Breaking up is hard to do

Posted on Aug 26th, 2019 - By Heather A. Van Epps

Nature Chemical Biology, Published online: 26 August 2019; doi:10.1038/s41589-019-0351-1A comprehensive genetic screen reveals new cellular trafficking factors and linker-dependent requirements for antibody–drug conjugate (ADC) cytotoxicity. These new insights may guide the design of optimized…

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Publisher Correction: Pharmacological targeting of the unfolded protein response for disease intervention

Posted on Aug 22nd, 2019 - By Claudio Hetz

Nature Chemical Biology, Published online: 22 August 2019; doi:10.1038/s41589-019-0363-xPublisher Correction: Pharmacological targeting of the unfolded protein response for disease…

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Switching on germination

Posted on Aug 19th, 2019 - By Caitlin Deane

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0358-7Switching on…

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Stick it to proteins

Posted on Aug 19th, 2019 - By Mirella Bucci

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0361-zStick it to…

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T(oo)bAd

Posted on Aug 19th, 2019 - By Priscille Brodin

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0347-xAn unusual terpene nucleoside, 1-TbAd, made by pathogenic mycobacteria acts as an antacid to block mycobacterial degradation in host cell vacuoles. The antacid activity acts to reduce acidity by neutralizing the pH of these degradative cell…

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Toll-like receptor mediated inflammation requires FASN-dependent MYD88 palmitoylation

Posted on Aug 19th, 2019 - By Young-Chan Kim

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0344-0Inhibition of fatty acid synthase, FASN, blocks innate immune signaling through TLR/MyD88 in neutrophils by blocking palmitoylation of MyD88 by palmitoyltransferase zDHHC6 and improves outcomes in two mouse models of…

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Breathing the same air

Posted on Aug 19th, 2019 - By Grant Miura

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0359-6Breathing the same…

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Lights, enzyme, action!

Posted on Aug 19th, 2019 - By Caitlin Deane

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0360-0Lights, enzyme,…

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Emerging structural insights into glycosyltransferase-mediated synthesis of glycans

Posted on Aug 19th, 2019 - By Kelley W. Moremen

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0350-2Analysis of recent X-ray crystallography data on eukaryotic glycosyltransferases in complex with acceptor and donor substrates reveals structural features that govern substrate specificity and glycosylation site…

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<i>Mycobacterium tuberculosis</i> releases an antacid that remodels phagosomes

Posted on Aug 19th, 2019 - By Jeffrey Buter

Nature Chemical Biology, Published online: 19 August 2019; doi:10.1038/s41589-019-0336-0Buter et al. elucidated the biological function of the terpene nucleoside 1-TbAd, which is made abundantly by virulent but not avirulent Mycobacterium tuberculosis strains, and demonstrate that 1-TbAd regulates the pH and function of host macrophage…

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Structure and chemistry of lysinoalanine crosslinking in the spirochaete flagella hook

Posted on Aug 12th, 2019 - By Michael J. Lynch

Nature Chemical Biology, Published online: 12 August 2019; doi:10.1038/s41589-019-0341-3Structural and biochemical characterization of the spirochaete flagellar hook protein FlgE reveals how cysteine and lysine residues spontaneously react to form an interdomain lysinoalanine crosslink without the involvement of additional…

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Convergent biosynthetic transformations to a bacterial specialized metabolite

Posted on Aug 12th, 2019 - By Yi-Ling Du

Nature Chemical Biology, Published online: 12 August 2019; doi:10.1038/s41589-019-0331-5The indolmycin biosynthetic pathway in a marine gram-negative bacterium is distinct from its counterpart in terrestrial gram-positive Streptomyces species, using a Streptomyces shunt product as a substrate for an N-demethylindolmycin…

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Inducible asymmetric cell division and cell differentiation in a bacterium

Posted on Aug 12th, 2019 - By Nikolai V. Mushnikov

Nature Chemical Biology, Published online: 12 August 2019; doi:10.1038/s41589-019-0340-4Small molecule or light-inducible gene circuits in Escherichia coli enable asymmetric cell pole localization of diguanylate phosphodiesterase and facilitate asymmetric cell division regulated by c-di-GMP-responsive transcription…

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A split CRISPR–Cpf1 platform for inducible genome editing and gene activation

Posted on Aug 12th, 2019 - By Yuta Nihongaki

Nature Chemical Biology, Published online: 12 August 2019; doi:10.1038/s41589-019-0338-ySplit Cpf1 pairs are identified to enable chemical- and light-induced genome editing via dimerization. Another pair of split Cpf1 can be used to activate gene expression with high efficiency in cells and in…

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A PCBP1–BolA2 chaperone complex delivers iron for cytosolic [2Fe–2S] cluster assembly

Posted on Aug 12th, 2019 - By Sarju J. Patel

Nature Chemical Biology, Published online: 12 August 2019; doi:10.1038/s41589-019-0330-6The iron chaperone poly(rC)-binding protein 1 (PCBP1) coordinates ferrous iron via its KH3 domain and, together with BolA2 and glutathione, forms a complex that is required for the assembly of [2Fe–2S] clusters on the cytosolic BolA2–Glrx3…

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Polar-opposite fates

Posted on Aug 12th, 2019 - By Helena R. Ma

Nature Chemical Biology, Published online: 12 August 2019; doi:10.1038/s41589-019-0337-zAsymmetric cell division, which generates daughter cells with distinct characteristics, is a mechanism for creating complex systems through cellular differentiation. Two studies in this issue develop synthetic platforms that program spatial localization of genetic material or signaling molecules to enable asymmetric cell division in Escherichia…

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A synthetic system for asymmetric cell division in <i>Escherichia coli</i>

Posted on Aug 12th, 2019 - By Sara Molinari

Nature Chemical Biology, Published online: 12 August 2019; doi:10.1038/s41589-019-0339-xThe chromosomal partitioning system (par) of Caulobacter crescentus was repurposed to create an inducible genetic circuit for asymmetric plasmid partitioning and cell division in Escherichia…

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Programmable RNA <i>N</i><sup>6</sup>-methyladenosine editing by CRISPR-Cas9 conjugates

Posted on Aug 5th, 2019 - By Xiao-Min Liu

Nature Chemical Biology, Published online: 05 August 2019; doi:10.1038/s41589-019-0327-1Fusion of Cas9 with m6A writers METTL3 and METTL14 or eraser ALKBH5 enables site-specific writing or erasing of RNA m6A modifications in mammalian cells and investigation of individual m6A modification-mediated…

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Site-specific m<sup>6</sup>A editing

Posted on Aug 5th, 2019 - By Jiangbo Wei

Nature Chemical Biology, Published online: 05 August 2019; doi:10.1038/s41589-019-0349-8The N6-methyladenosine modification on RNA affects almost all steps of RNA metabolism. A new approach, using the CRISPR-based technology to modulate m6A level in mRNA, enables direct functional interrogation of site-specific…

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Sweetly profiling the cysteinome

Posted on Aug 5th, 2019 - By Jing Yang

Nature Chemical Biology, Published online: 05 August 2019; doi:10.1038/s41589-019-0348-9A new sugar-based cysteine-reactive probe, combined with competitive activity-based protein profiling (ABPP), enables site-centric target deconvolution of itaconate in native proteomes, shedding light on a novel mechanism of action for this important immunoregulatory metabolite in inflammatory…

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2-Hydroxyacyl-CoA lyase catalyzes acyloin condensation for one-carbon bioconversion

Posted on Aug 5th, 2019 - By Alexander Chou

Nature Chemical Biology, Published online: 05 August 2019; doi:10.1038/s41589-019-0328-0A bacterial 2-hydroxyacyl-CoA lyase catalyzes ligation of carbonyl-containing molecules of different chain lengths with formyl-CoA to produce elongated 2-hydroxyacyl-CoAs, enabling a one-carbon bioconversion pathway with formaldehyde as a…

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S-glycosylation-based cysteine profiling reveals regulation of glycolysis by itaconate

Posted on Jul 22nd, 2019 - By Wei Qin

Nature Chemical Biology, Published online: 22 July 2019; doi:10.1038/s41589-019-0323-5Using a thiol-reactive probe, chemoproteomic profiling of cysteine targets of itaconate reveals the covalent modification of glycolytic enzymes, impairing glycolytic flux and contributing to attenuation of the inflammatory response in…

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Imaging nonsense

Posted on Jul 18th, 2019 - By Yiyun Song

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0333-3Imaging…

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Pharmacological targeting of the unfolded protein response for disease intervention

Posted on Jul 18th, 2019 - By Claudio Hetz

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0326-2Hetz et al. discuss recent advances in the identification and optimization of small molecules targeting the unfolded protein response and the application of these small molecules in cancers, neurodegeneration and metabolic…

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DNA jumps with CRISPR

Posted on Jul 18th, 2019 - By Yiyun Song

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0335-1DNA jumps with…

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Freedom to bind

Posted on Jul 18th, 2019 - By Mirella Bucci

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0332-4Freedom to…

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A programmable DNA-origami platform for studying lipid transfer between bilayers

Posted on Jul 18th, 2019 - By Xin Bian

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0325-3Use of DNA-origami nanostructures to study lipid transfer between closely apposed membrane bilayers supports a model where phospholipids are transferred by extended synaptotagmin 1 between the endoplasmic reticulum and plasma membrane through a shuttle…

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PROSPECTing for drugs

Posted on Jul 18th, 2019 - By Grant Miura

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0334-2PROSPECTing for…

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Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases

Posted on Jul 18th, 2019 - By Matthew Ravalin

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0322-6The C termini sequences recognized by E3 ubiquitin ligase CHIP were identified via a peptide library screen. Caspase cleavage caused the exposure of aspartic acid at the C termini of Tau and caspase-6 that made them accessible to…

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An excreted small molecule promotes <i>C. elegans</i> reproductive development and aging

Posted on Jul 18th, 2019 - By Andreas H. Ludewig

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0321-7Male C. elegans excrete an N-acylated glutamine that acts via evolutionarily conserved nuclear hormone receptor and chemosensory pathways to counteract dauer diapause and accelerate sexual maturation of hermaphrodites, at the cost of shortening hermaphrodite…

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Covalent targeting of the vacuolar H<sup>+</sup>-ATPase activates autophagy via mTORC1 inhibition

Posted on Jul 8th, 2019 - By Clive Yik-Sham Chung

Nature Chemical Biology, Published online: 08 July 2019; doi:10.1038/s41589-019-0308-4A covalent ligand that targets C277 of ATP6V1A was identified resulting in enhanced v-ATPase activity, inhibition of mTORC1 signaling, increased lysosomal acidification, activation of autophagy and clearance of toxic protein…

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Fragment-based discovery of a chemical probe for the PWWP1 domain of NSD3

Posted on Jul 8th, 2019 - By Jark Böttcher

Nature Chemical Biology, Published online: 08 July 2019; doi:10.1038/s41589-019-0310-xA chemical probe BI-9321 for the PWWP1 domain of NSD3 and its inactive analog were identified. BI-9321 binds to the methyl-lysine binding site, reduces the association of NSD3 with chromatin and inhibits proliferation of acute myeloid leukemia…

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A marine bacterial enzymatic cascade degrades the algal polysaccharide ulvan

Posted on Jul 8th, 2019 - By Lukas Reisky

Nature Chemical Biology, Published online: 08 July 2019; doi:10.1038/s41589-019-0311-9Elucidation of a multi-enzyme pathway for degradation of the polysaccharide ulvan by Formosa agariphila provides tools to use ulvan biomass from marine algal blooms as feedstock for renewable sources of…

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Clearing debris

Posted on Jul 8th, 2019 - By Delong Meng

Nature Chemical Biology, Published online: 08 July 2019; doi:10.1038/s41589-019-0320-8A new small molecule that targets the vacuolar H+-ATPase activates autophagy, inhibits mTORC1 signaling, and displays potential for clearing toxic protein aggregates involved in neurodegenerative…

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Publisher Correction: BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design

Posted on Jul 2nd, 2019 - By William Farnaby

Nature Chemical Biology, Published online: 02 July 2019; doi:10.1038/s41589-019-0329-zPublisher Correction: BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC…

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The cholesterol transfer protein GRAMD1A regulates autophagosome biogenesis

Posted on Jun 20th, 2019 - By Luca Laraia

Nature Chemical Biology, Published online: 20 June 2019; doi:10.1038/s41589-019-0307-5The cholesterol-transfer protein GRAMD1A is identified as the target of the autophagy inhibitors autogramin-1 and autogramin-2. GRAMD1A is found to be required for autophagosome…

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Lipids lead the way

Posted on Jun 20th, 2019 - By Leslie N. Aldrich

Nature Chemical Biology, Published online: 20 June 2019; doi:10.1038/s41589-019-0309-3Autophagy is a ‘self-eating’ recycling process that maintains cellular homeostasis. Autogramins were identified as small-molecule autophagy inhibitors that target the cholesterol transport protein GRAMD1A, revealing a role for cholesterol in autophagosome…

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A small-molecule inhibitor of C5 complement protein

Posted on Jun 17th, 2019 - By Keith Jendza

Nature Chemical Biology, Published online: 17 June 2019; doi:10.1038/s41589-019-0303-9An inhibitor of the complement pathway of the innate immune system targets the human complement component 5 protein (C5) by binding to an interfacial pocket to prevent its proteolytic cleavage by the last enzyme of the complement pathway, C5…

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Stick it to E3s

Posted on Jun 17th, 2019 - By Matthias Brand

Nature Chemical Biology, Published online: 17 June 2019; doi:10.1038/s41589-019-0312-8The limited availability of small-molecule ligands for E3 ubiquitin ligases stymies the development of next-generation degraders. Two recent papers report the identification of novel, covalent and PROTAC-compatible ligands that hijack the previously untargeted ligases RNF114 and…

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Engineering of an oleaginous bacterium for the production of fatty acids and fuels

Posted on Jun 17th, 2019 - By Hye Mi Kim

Nature Chemical Biology, Published online: 17 June 2019; doi:10.1038/s41589-019-0295-5Optimization of triacylglycerol production in the oleaginous bacterium Rhodococcus opacus followed by pathway engineering enables the enhanced production of free fatty acids, fatty acid ethyl esters and long-chain hydrocarbons from…

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The RASER’s edge

Posted on Jun 17th, 2019 - By Grant Miura

Nature Chemical Biology, Published online: 17 June 2019; doi:10.1038/s41589-019-0317-3The RASER’s…

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Molecular basis for interactions between an acyl carrier protein and a ketosynthase

Posted on Jun 17th, 2019 - By Jacob C. Milligan

Nature Chemical Biology, Published online: 17 June 2019; doi:10.1038/s41589-019-0301-yA combination of crosslinking, X-ray crystallography, NMR, and mutagenesis provide a detailed visualization of the interactions between an acyl carrier protein and β-ketoacyl-ACP-synthase I in the Escherchia coli fatty acid synthase…

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TEThered vitamin C

Posted on Jun 17th, 2019 - By Yiyun Song

Nature Chemical Biology, Published online: 17 June 2019; doi:10.1038/s41589-019-0319-1TEThered vitamin…

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Harnessing the anti-cancer natural product nimbolide for targeted protein degradation

Posted on Jun 17th, 2019 - By Jessica N. Spradlin

Nature Chemical Biology, Published online: 17 June 2019; doi:10.1038/s41589-019-0304-8The natural product nimbolide covalently reacts with a functional cysteine of the E3 ubiquitin ligase RNF114, resulting in impaired substrate recognition and degradation, enabling the use of nimbolide for targeted protein…

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Come-hither compounds

Posted on Jun 17th, 2019 - By Caitlin Deane

Nature Chemical Biology, Published online: 17 June 2019; doi:10.1038/s41589-019-0316-4Come-hither…

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BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design

Posted on Jun 10th, 2019 - By William Farnaby

Nature Chemical Biology, Published online: 10 June 2019; doi:10.1038/s41589-019-0294-6A structure-based design allows the development of a potent PROTAC to degrade BAF ATPase subunits SMARCA2 and SMARCA4 via recruitment of E3 ubiquitin ligase VHL and induce cancer cell…

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Author Correction: Mitochondrial metabolism promotes adaptation to proteotoxic stress

Posted on Jun 4th, 2019 - By Peter Tsvetkov

Nature Chemical Biology, Published online: 04 June 2019; doi:10.1038/s41589-019-0315-5Author Correction: Mitochondrial metabolism promotes adaptation to proteotoxic…

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Mitochondrial metabolism promotes adaptation to proteotoxic stress

Posted on May 27th, 2019 - By Peter Tsvetkov

Nature Chemical Biology, Published online: 27 May 2019; doi:10.1038/s41589-019-0291-9Mitochondrial energy metabolism regulates proteotoxic stress tolerance, exposing a newly discovered sensitivity to the small molecule elesclomol, which induces FDX1-mediated, copper-dependent cell…

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Rewiring bacterial two-component systems by modular DNA-binding domain swapping

Posted on May 20th, 2019 - By Sebastian R. Schmidl

Nature Chemical Biology, Published online: 20 May 2019; doi:10.1038/s41589-019-0286-6Rewiring of bacterial two-component systems (TCSs) was achieved by DNA-binding domain swapping of the two largest response regulator families, which enables cross-species porting and provides a tool for identifying ligands for uncharacterized…

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Small-molecule control of antibody N-glycosylation in engineered mammalian cells

Posted on May 20th, 2019 - By Michelle M. Chang

Nature Chemical Biology, Published online: 20 May 2019; doi:10.1038/s41589-019-0288-4Synthetic gene circuits regulated by small molecules have been used to fine-tune glycosyltransferase expression in CHO cells, providing a method to produce therapeutic monoclonal antibodies with precise glycosylation…

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Natural fumigation as a mechanism for volatile transport between flower organs

Posted on May 17th, 2019 - By Benoît Boachon

Nature Chemical Biology, Published online: 17 May 2019; doi:10.1038/s41589-019-0287-5Bioactive sesquiterpenes accumulating in petunia stigmas are synthesized in the floral tube and then transported to the pistil via natural fumigation within the internal airspace of the developing…

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Suicide inactivation of the uracil DNA glycosylase UdgX by covalent complex formation

Posted on May 17th, 2019 - By Jie Tu

Nature Chemical Biology, Published online: 17 May 2019; doi:10.1038/s41589-019-0290-xStructural analysis of uracil DNA glycosylase reveals that its high affinity with DNA substrates derives from a stable intermediate that is formed by conservative H109 in a protruding loop covalently binding to the abasic site after uracil is…

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The new face of nanowires

Posted on May 17th, 2019 - By Caitlin Deane

Nature Chemical Biology, Published online: 17 May 2019; doi:10.1038/s41589-019-0299-1The new face of…

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Arrestin-g pain

Posted on May 17th, 2019 - By Mirella Bucci

Nature Chemical Biology, Published online: 17 May 2019; doi:10.1038/s41589-019-0300-zArrestin-g…

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Covalent binding of uracil DNA glycosylase UdgX to abasic DNA upon uracil excision

Posted on May 17th, 2019 - By Woo-Chan Ahn

Nature Chemical Biology, Published online: 17 May 2019; doi:10.1038/s41589-019-0289-3Structural analysis of uracil DNA glycosylases in complex with DNA reveals that conserved H109 acts as a nucleophile to attack the oxocarbenium ion and makes a covalent bond to the abasic site after uracil excision to form a stable…

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Structural and mechanistic basis of mammalian Nudt12 RNA deNADding

Posted on May 17th, 2019 - By Ewa Grudzien-Nogalska

Nature Chemical Biology, Published online: 17 May 2019; doi:10.1038/s41589-019-0293-7Structural and biochemical analyses identify Nudt12 as a novel mRNA deNADing enzyme in mammalian cells, which has a different substrate preference compared to the deNADing enzyme…

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Substrate-selective inhibitors that reprogram the activity of insulin-degrading enzyme

Posted on May 13th, 2019 - By Juan Pablo Maianti

Substrate-selective inhibitors that reprogram the activity of insulin-degrading enzymeNature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0271-0High-throughput screening identifies compounds that target insulin-degrading enzyme (IDE) and X-ray co-crystallography reveals how these compounds block insulin degradation by IDE but support its proteolysis of other substrates, including…

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Author Correction: In-solution enrichment identifies peptide inhibitors of protein–protein interactions

Posted on May 13th, 2019 - By Fayçal Touti

Author Correction: In-solution enrichment identifies peptide inhibitors of protein–protein interactionsNature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0302-xAuthor Correction: In-solution enrichment identifies peptide inhibitors of protein–protein…

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Walking over the inflammasome

Posted on May 13th, 2019 - By Oliver Gorka

Walking over the inflammasomeNature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0292-8The NLRP3 inflammasome contributes to pathogenic inflammation in a broad range of diseases, making it a highly relevant drug target. Two studies published in this issue found an inhibitor of NLRP3 inflammasome activation to directly bind NLRP3 within its central NACHT domain, interfering with ATP hydrolysis and structural changes critical for NLRP3 oligomerization and subsequent…

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MCC950 closes the active conformation of NLRP3 to an inactive state

Posted on May 13th, 2019 - By Ana Tapia-Abellán

MCC950 closes the active conformation of NLRP3 to an inactive stateNature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0278-6MCC950, a small-molecule inhibitor of the NLRP3 inflammasome, inactivates NLRP3, including hyperactive disease-linked mutations, by closing the ‘open’ conformation, thereby preventing conformational changes required for NLRP3…

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Light-based control of metabolic flux through assembly of synthetic organelles

Posted on May 13th, 2019 - By Evan M. Zhao

Light-based control of metabolic flux through assembly of synthetic organellesNature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0284-8Optogenetically controlling the assembly of enzyme clusters enhances product formation and specificity during deoxyviolacein biosynthesis by decreasing concentrations of intermediate metabolites and reducing flux through competing…

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MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition

Posted on May 13th, 2019 - By Rebecca C. Coll

MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibitionNature Chemical Biology, Published online: 13 May 2019; doi:10.1038/s41589-019-0277-7MCC950, a small-molecule inhibitor of the NLRP3 inflammasome, interacts directly with NLRP3 at the Walker B motif that hydrolyzes ATP, as defined by a protease-susceptibility assay, mutational analysis, and surface plasmon resonance…

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Author Correction: Affinity-based capture and identification of protein effectors of the growth regulator ppGpp

Posted on May 10th, 2019 - By Boyuan Wang

Author Correction: Affinity-based capture and identification of protein effectors of the growth regulator ppGppNature Chemical Biology, Published online: 10 May 2019; doi:10.1038/s41589-019-0296-4Author Correction: Affinity-based capture and identification of protein effectors of the growth regulator…

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Glycan sulfation patterns define autophagy flux at axon tip via PTPRσ-cortactin axis

Posted on May 6th, 2019 - By Kazuma Sakamoto

Glycan sulfation patterns define autophagy flux at axon tip via PTPRσ-cortactin axisGlycan sulfation patterns define autophagy flux at axon tip via PTPRσ-cortactin axis, Published online: 06 May 2019; doi:10.1038/s41589-019-0274-xSulfation of chondroitin sulfate and heparan sulfate dictates their abilities to promote axon growth via regulating the binding to the phosphatase PTPRσ and the consequences on phosphorylation of the cortactin component of the autophagy…

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