Neopinone isomerase is involved in codeine and morphine biosynthesis in opium poppy

Posted on Mar 18th, 2019 - By Mehran Dastmalchi

Neopinone isomerase is involved in codeine and morphine biosynthesis in opium poppyNeopinone isomerase is involved in codeine and morphine biosynthesis in opium poppy, Published online: 18 March 2019; doi:10.1038/s41589-019-0247-0Neopinone isomerase catalyzes the isomerization of the opiate alkaloid neopinone to codeinone, driving the biosynthesis of codeine and morphine and preventing accumulation of their isomers neopine and…

Continue Reading

A better binder builder

Posted on Mar 18th, 2019 - By Caitlin Deane

A better binder builderA better binder builder, Published online: 18 March 2019; doi:10.1038/s41589-019-0258-xA better binder…

Continue Reading

Dual phenazine gene clusters enable diversification during biosynthesis

Posted on Mar 18th, 2019 - By Yi-Ming Shi

Dual phenazine gene clusters enable diversification during biosynthesisDual phenazine gene clusters enable diversification during biosynthesis, Published online: 18 March 2019; doi:10.1038/s41589-019-0246-1Enzymes from two discrete biosynthetic gene clusters in the entomopathogenic bacterium Xenorhabdus szentirmaii cooperate to produce a diverse array of phenazine natural products, including phenazine–peptide and phenazine–polyketide…

Continue Reading

New roles for old RNA cap flavors

Posted on Mar 18th, 2019 - By Richard A. Padgett

New roles for old RNA cap flavorsNew roles for old RNA cap flavors, Published online: 18 March 2019; doi:10.1038/s41589-019-0252-3The N6-methyladenosine modification next to the 5′ RNA cap has dynamic regulatory functions. Recent findings show that this modification regulates the splicing and translational activity of different classes of…

Continue Reading

Affinity selection and sequencing

Posted on Mar 18th, 2019 - By Kit S. Lam

Affinity selection and sequencingAffinity selection and sequencing, Published online: 18 March 2019; doi:10.1038/s41589-019-0253-2Powerful combinatorial peptide library methods allow the discovery of peptide leads from diverse libraries. A new platform based on tandem mass spectrometry peptide sequencing coupled with high-performance size-exclusion chromatography enables identification of high-affinity peptidic ligands from focused…

Continue Reading

An appetite for aromatics

Posted on Mar 18th, 2019 - By Mirella Bucci

An appetite for aromaticsAn appetite for aromatics, Published online: 18 March 2019; doi:10.1038/s41589-019-0260-3An appetite for…

Continue Reading

A broken heart can mend

Posted on Mar 18th, 2019 - By Grant Miura

A broken heart can mendA broken heart can mend, Published online: 18 March 2019; doi:10.1038/s41589-019-0259-9A broken heart can…

Continue Reading

A new CRISPR scissor

Posted on Mar 18th, 2019 - By Yiyun Song

A new CRISPR scissorA new CRISPR scissor, Published online: 18 March 2019; doi:10.1038/s41589-019-0261-2A new CRISPR…

Continue Reading

Addendum: A cellular chemical probe targeting the chromodomains of Polycomb repressive complex 1

Posted on Mar 6th, 2019 - By Jacob I Stuckey

Addendum: A cellular chemical probe targeting the chromodomains of Polycomb repressive complex 1Addendum: A cellular chemical probe targeting the chromodomains of Polycomb repressive complex 1, Published online: 06 March 2019; doi:10.1038/s41589-019-0242-5Addendum: A cellular chemical probe targeting the chromodomains of Polycomb repressive complex…

Continue Reading

A flexible filter maintains a tight grip

Posted on Mar 4th, 2019 - By Adrian Gross

A flexible filter maintains a tight gripA flexible filter maintains a tight grip, Published online: 04 March 2019; doi:10.1038/s41589-019-0248-zPotassium channels allow the passage of potassium ions across membranes at rates approaching the diffusion limit while maintaining exquisite selectivity between ion species. Single-molecule studies now reveal that the selectivity filter of these proteins transitions between different…

Continue Reading

Potassium channel selectivity filter dynamics revealed by single-molecule FRET

Posted on Mar 4th, 2019 - By Shizhen Wang

Potassium channel selectivity filter dynamics revealed by single-molecule FRETPotassium channel selectivity filter dynamics revealed by single-molecule FRET, Published online: 04 March 2019; doi:10.1038/s41589-019-0240-7Single-molecule FRET shows that a loop, which forms the selectivity filter in the bacterial inwardly rectifying K+ channel KirBac1.1, transitions between constrained and dilated conformations depending on ion occupancy of the…

Continue Reading

Publisher Correction: PH-domain-binding inhibitors of nucleotide exchange factor BRAG2 disrupt Arf GTPase signaling

Posted on Mar 4th, 2019 - By Agata Nawrotek

Publisher Correction: PH-domain-binding inhibitors of nucleotide exchange factor BRAG2 disrupt Arf GTPase signalingPublisher Correction: PH-domain-binding inhibitors of nucleotide exchange factor BRAG2 disrupt Arf GTPase signaling, Published online: 04 March 2019; doi:10.1038/s41589-019-0255-0Publisher Correction: PH-domain-binding inhibitors of nucleotide exchange factor BRAG2 disrupt Arf GTPase…

Continue Reading

Bidirectional modulation of HIF-2 activity through chemical ligands

Posted on Feb 25th, 2019 - By Dalei Wu

Bidirectional modulation of HIF-2 activity through chemical ligandsBidirectional modulation of HIF-2 activity through chemical ligands, Published online: 25 February 2019; doi:10.1038/s41589-019-0234-5Structural analysis of HIF-2α in complex with agonists and antagonists reveal that chemical ligands regulate the activity of HIF-2α by affecting the stability of the HIF-2α–ARNT heterodimer via redirecting residues in the PAS-B…

Continue Reading

Designing a chemical inhibitor for the AAA protein spastin using active site mutations

Posted on Feb 18th, 2019 - By Tommaso Cupido

Designing a chemical inhibitor for the AAA protein spastin using active site mutationsDesigning a chemical inhibitor for the AAA protein spastin using active site mutations, Published online: 18 February 2019; doi:10.1038/s41589-019-0225-6The AAA protein spastin is needed for cell division and organelle transport. Testing spastin constructs with engineered mutations resulted in the identification of a chemical probe to analyze spastin-specific functions in…

Continue Reading

Tightening a deadly pore former

Posted on Feb 18th, 2019 - By Jialing Lin

Tightening a deadly pore formerTightening a deadly pore former, Published online: 18 February 2019; doi:10.1038/s41589-019-0235-4A small molecule was identified that binds to a unique site on the pro-apoptotic protein BAX, stabilizing the protein structure allosterically and preventing the conformational activation to a pore former by BH3…

Continue Reading

FTO controls reversible m<sup>6</sup>Am RNA methylation during snRNA biogenesis

Posted on Feb 18th, 2019 - By Jan Mauer

FTO controls reversible m6Am RNA methylation during snRNA biogenesisFTO controls reversible m<sup>6</sup>Am RNA methylation during snRNA biogenesis, Published online: 18 February 2019; doi:10.1038/s41589-019-0231-8Two different methylation states of the adenosine adjacent to the snRNA cap are found in the biogenesis process of snRNAs, Am and m6Am, whose levels are regulated by FTO and are related to alternative pre-mRNA…

Continue Reading

METTLing with translation

Posted on Feb 15th, 2019 - By Grant Miura

METTLing with translationMETTLing with translation, Published online: 15 February 2019; doi:10.1038/s41589-019-0237-2METTLing with…

Continue Reading

To be or not to be?

Posted on Feb 15th, 2019 - By Yiyun Song

To be or not to be?To be or not to be?, Published online: 15 February 2019; doi:10.1038/s41589-019-0239-0To be or not to…

Continue Reading

Site-specific ubiquitylation and SUMOylation using genetic-code expansion and sortase

Posted on Feb 15th, 2019 - By Maximilian Fottner

Site-specific ubiquitylation and SUMOylation using genetic-code expansion and sortaseSite-specific ubiquitylation and SUMOylation using genetic-code expansion and sortase, Published online: 15 February 2019; doi:10.1038/s41589-019-0227-4A method combining genetic-code expansion, bioorthogonal Staudinger reduction and sortase-mediated transpeptidation enables site-specific and orthogonal modification of proteins with ubiquitin and SUMO in vitro and in living…

Continue Reading

A super-powered S-layer

Posted on Feb 15th, 2019 - By Caitlin Deane

A super-powered S-layerA super-powered S-layer, Published online: 15 February 2019; doi:10.1038/s41589-019-0236-3A super-powered…

Continue Reading

Decoding without the cipher

Posted on Feb 15th, 2019 - By Amit Kumar Singh Gautam

Decoding without the cipherDecoding without the cipher, Published online: 15 February 2019; doi:10.1038/s41589-019-0230-9A new method introduces ubiquitin or ubiquitin-like proteins at specific sites in any protein without the requirement of the cellular ubiquitylation machinery. This will help decipher the code by which these modifications control cellular…

Continue Reading

Author Correction: Complete reconstitution of the diverse pathways of gentamicin B biosynthesis

Posted on Feb 6th, 2019 - By Yeon Hee Ban

Author Correction: Complete reconstitution of the diverse pathways of gentamicin B biosynthesisAuthor Correction: Complete reconstitution of the diverse pathways of gentamicin B biosynthesis, Published online: 06 February 2019; doi:10.1038/s41589-019-0232-7Author Correction: Complete reconstitution of the diverse pathways of gentamicin B…

Continue Reading

A class of highly selective inhibitors bind to an active state of PI3Kγ

Posted on Feb 4th, 2019 - By Gangadhara Gangadhara

A class of highly selective inhibitors bind to an active state of PI3KγA class of highly selective inhibitors bind to an active state of PI3Kγ, Published online: 04 February 2019; doi:10.1038/s41589-018-0215-0Combining X-ray structures, surface plasmon resonance and hydrogen-deuterium exchange–mass spectrometry, a class of highly selective inhibitors was found to bind to an active state of PI3Kγ breaking a conformational ‘lock’ important for activation of…

Continue Reading

Mechanism of regulation and neutralization of the AtaR–AtaT toxin–antitoxin system

Posted on Feb 4th, 2019 - By Dukas Jurėnas

Mechanism of regulation and neutralization of the AtaR–AtaT toxin–antitoxin systemMechanism of regulation and neutralization of the AtaR–AtaT toxin–antitoxin system, Published online: 04 February 2019; doi:10.1038/s41589-018-0216-zStructural and biochemical analysis of the AtaR–AtaT toxin–antioxin system reveals that AtaR traps AtaT in a precatalytic monomeric state and forms a heterohexameric complex to neutralize AtaT and repress transcription of the…

Continue Reading

Small-molecule allosteric inhibitors of BAX

Posted on Feb 4th, 2019 - By Thomas P. Garner

Small-molecule allosteric inhibitors of BAXSmall-molecule allosteric inhibitors of BAX, Published online: 04 February 2019; doi:10.1038/s41589-018-0223-0Using biochemical and NMR studies, a class of small-molecule inhibitors termed BAX activation inhibitors were found to bind directly to a previously unrecognized pocket of inactive BAX and allosterically inhibit conformational changes in…

Continue Reading

A chemoproteomic portrait of the oncometabolite fumarate

Posted on Feb 4th, 2019 - By Rhushikesh A. Kulkarni

A chemoproteomic portrait of the oncometabolite fumarateA chemoproteomic portrait of the oncometabolite fumarate, Published online: 04 February 2019; doi:10.1038/s41589-018-0217-yChemoproteomic mapping of fumarate sensitive cysteines in a hereditary leiomyomatosis and renal cell carcinoma cell line revealed a critical cysteine in the protein–protein interaction interface of the SWI–SNF…

Continue Reading

Bacterial sensors define intracellular free energies for correct enzyme metalation

Posted on Jan 28th, 2019 - By Deenah Osman

Bacterial sensors define intracellular free energies for correct enzyme metalationBacterial sensors define intracellular free energies for correct enzyme metalation, Published online: 28 January 2019; doi:10.1038/s41589-018-0211-4The sensitivities of a set of bacterial metal-sensing transcriptional regulators explain how a protein, such as the cobalt chelatase CbiK, is metalated with its cognate metal in cells rather than mis-metalated with more tightly binding…

Continue Reading

Combined chemosensitivity and chromatin profiling prioritizes drug combinations in CLL

Posted on Jan 28th, 2019 - By Christian Schmidl

Combined chemosensitivity and chromatin profiling prioritizes drug combinations in CLLCombined chemosensitivity and chromatin profiling prioritizes drug combinations in CLL, Published online: 28 January 2019; doi:10.1038/s41589-018-0205-2Epigenome profiling in combination with imaging-based chemosensitivity and integrative bioinformatic analysis establishes a method for detecting therapy-induced vulnerabilities, as shown here for ibrutinib-treated chronic lymphocytic…

Continue Reading

An allosteric MALT1 inhibitor is a molecular corrector rescuing function in an immunodeficient patient

Posted on Jan 28th, 2019 - By Jean Quancard

An allosteric MALT1 inhibitor is a molecular corrector rescuing function in an immunodeficient patientAn allosteric MALT1 inhibitor is a molecular corrector rescuing function in an immunodeficient patient, Published online: 28 January 2019; doi:10.1038/s41589-018-0222-1An allosteric inhibitor of the proteolytic activity of the CBM signalosome complex scaffolding protein MALT1 acts as a pharmacological chaperone to stabilize a mutant MALT1 carried by an immunodeficient…

Continue Reading

Freedom of movement

Posted on Jan 21st, 2019 - By Ulrich Rass

Freedom of movementFreedom of movement, Published online: 21 January 2019; doi:10.1038/s41589-019-0224-7Holliday junction resolvases lock dynamic DNA four-way junctions into specific structural conformations for symmetric DNA cleavage. Single-molecule studies now reveal that resolvases can relax their grip, enabling Holliday junction conformer transitions and branch migration in the enzyme-bound…

Continue Reading

Junction resolving enzymes use multivalency to keep the Holliday junction dynamic

Posted on Jan 21st, 2019 - By Ruobo Zhou

Junction resolving enzymes use multivalency to keep the Holliday junction dynamicJunction resolving enzymes use multivalency to keep the Holliday junction dynamic, Published online: 21 January 2019; doi:10.1038/s41589-018-0209-ySingle-molecule analysis reveals a novel binding state of Holliday junction (HJ) resolving enzymes where the enzymes partially dissociate from the HJ and allowing nearly unencumbered HJ dynamics, suggesting coupled branch migration and HJ…

Continue Reading

Sequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicum

Posted on Jan 21st, 2019 - By Xiaoxue Zhou

Sequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicumSequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicum, Published online: 21 January 2019; doi:10.1038/s41589-018-0206-1Assembly of the mycobacterial cell envelope layers, including peptidoglycan (PG) and the mycomembrane (MM), is synchronous during elongation, when a mobile fraction of the MM diffuses into the septum after thinning of the diffusion barrier…

Continue Reading

A new Tar-get for inhibition

Posted on Jan 18th, 2019 - By Mirella Bucci

A new Tar-get for inhibitionA new Tar-get for inhibition, Published online: 18 January 2019; doi:10.1038/s41589-018-0220-3A new Tar-get for…

Continue Reading

Pass it along

Posted on Jan 18th, 2019 - By Yiyun Song

Pass it alongPass it along, Published online: 18 January 2019; doi:10.1038/s41589-018-0221-2Pass it…

Continue Reading

Cutting in choline

Posted on Jan 18th, 2019 - By Caitlin Deane

Cutting in cholineCutting in choline, Published online: 18 January 2019; doi:10.1038/s41589-018-0218-xCutting in…

Continue Reading

Ras tuning

Posted on Jan 18th, 2019 - By Grant Miura

Ras tuningRas tuning, Published online: 18 January 2019; doi:10.1038/s41589-018-0219-9Ras…

Continue Reading

Molecular tools for imaging and recording neuronal activity

Posted on Jan 18th, 2019 - By Wenjing Wang

Molecular tools for imaging and recording neuronal activityMolecular tools for imaging and recording neuronal activity, Published online: 18 January 2019; doi:10.1038/s41589-018-0207-0A collection of genetically encoded tools, each with their own capabilities, limitations and performance characteristics, are available for monitoring and manipulating neuronal activity that could allow visualizing the brain at single-cell…

Continue Reading

Selective and reversible modification of kinase cysteines with chlorofluoroacetamides

Posted on Jan 14th, 2019 - By Naoya Shindo

Selective and reversible modification of kinase cysteines with chlorofluoroacetamidesSelective and reversible modification of kinase cysteines with chlorofluoroacetamides, Published online: 14 January 2019; doi:10.1038/s41589-018-0204-3Discovery and exploitation of inherent reaction features of chlorofluoroacetamide (CFA) as a warhead such as low off-target activity and reversible reactivity with cysteine enable specific covalent inhibition of targeted…

Continue Reading

Complete reconstitution of the diverse pathways of gentamicin B biosynthesis

Posted on Jan 14th, 2019 - By Yeon Hee Ban

Complete reconstitution of the diverse pathways of gentamicin B biosynthesisComplete reconstitution of the diverse pathways of gentamicin B biosynthesis, Published online: 14 January 2019; doi:10.1038/s41589-018-0203-4The reconstitution of gentamicin B biosynthesis reveals the existence of multiple new intermediates and branching pathways and enables the identification of factors that contribute to the low levels of the natural product in the native…

Continue Reading

Fast bioelectrical switches

Posted on Jan 14th, 2019 - By Michaela TerAvest

Fast bioelectrical switchesFast bioelectrical switches, Published online: 14 January 2019; doi:10.1038/s41589-018-0212-3Faster-than-transcription control of cellular activities is an important but challenging engineering target. Using split ferredoxins and induced dimerization or conformational changes, newly developed metalloprotein switches provide a fast method to control electron…

Continue Reading

A chemical–genetic screen identifies ABHD12 as an oxidized-phosphatidylserine lipase

Posted on Jan 14th, 2019 - By Dhanashree S. Kelkar

A chemical–genetic screen identifies ABHD12 as an oxidized-phosphatidylserine lipaseA chemical–genetic screen identifies ABHD12 as an oxidized-phosphatidylserine lipase, Published online: 14 January 2019; doi:10.1038/s41589-018-0195-0Screening with a small-molecule reactive-oxygen-species generator identifies the serine hydrolase enzyme ABHD12 as a lipase for the proapoptotic oxidized phoshatidylserine (ox-PS) lipids, which trigger production of proinflammatory…

Continue Reading

Discovery of a ZIP7 inhibitor from a Notch pathway screen

Posted on Jan 14th, 2019 - By Erin Nolin

Discovery of a ZIP7 inhibitor from a Notch pathway screenDiscovery of a ZIP7 inhibitor from a Notch pathway screen, Published online: 14 January 2019; doi:10.1038/s41589-018-0200-7A cell-based phenotypic screen identifying inhibitors of Notch signaling led to the discovery of NVS-ZP7-4, which blocks the activity of the zinc transporter SLC39a7 (ZIP7) and induces cell death through an ER stress…

Continue Reading

IFITM3 directly engages and shuttles incoming virus particles to lysosomes

Posted on Jan 14th, 2019 - By Jennifer S. Spence

IFITM3 directly engages and shuttles incoming virus particles to lysosomesIFITM3 directly engages and shuttles incoming virus particles to lysosomes, Published online: 14 January 2019; doi:10.1038/s41589-018-0213-2Live-cell imaging and virus trafficking studies show that the host innate immune receptor IFITM3 localizes with endocytic vesicles that fuse with incoming viruses to ultimately enhance their traffic to…

Continue Reading

A genetics-free method for high-throughput discovery of cryptic microbial metabolites

Posted on Jan 7th, 2019 - By Fei Xu

A genetics-free method for high-throughput discovery of cryptic microbial metabolitesA genetics-free method for high-throughput discovery of cryptic microbial metabolites, Published online: 07 January 2019; doi:10.1038/s41589-018-0193-2A combination of elicitor screening to induce expression of silent biosynthetic gene clusters with imaging mass spectrometry to visualize the resulting metabolome enables the discovery of nine cryptic natural…

Continue Reading

<i>Legionella</i> effector SetA as a general O-glucosyltransferase for eukaryotic proteins

Posted on Jan 7th, 2019 - By Ling Gao

Legionella effector SetA as a general O-glucosyltransferase for eukaryotic proteins<i>Legionella</i> effector SetA as a general O-glucosyltransferase for eukaryotic proteins, Published online: 07 January 2019; doi:10.1038/s41589-018-0189-yA chemoenzymatic tagging approach was developed and identified eukaryotic host proteins that are O-glycosylated by SetA from Legionella. The SetA-consensus motif was applied to recombinant proteins yielding a site-specific O-glucosylation…

Continue Reading

Protein circuits reprogram cells

Posted on Jan 7th, 2019 - By Yiqian Wu

Protein circuits reprogram cellsProtein circuits reprogram cells, Published online: 07 January 2019; doi:10.1038/s41589-018-0210-5Two protein circuit systems, split-protease-cleavable orthogonal coiled-coil logic (SPOC logic) and circuits of hacked orthogonal modular proteases (CHOMP), have been developed to permit rapid and logic function-based control of mammalian cellular…

Continue Reading

Targeted delivery of nitric oxide via a ‘bump-and-hole’-based enzyme–prodrug pair

Posted on Dec 31st, 2018 - By Jingli Hou

Targeted delivery of nitric oxide via a ‘bump-and-hole’-based enzyme–prodrug pairTargeted delivery of nitric oxide via a ‘bump-and-hole’-based enzyme–prodrug pair, Published online: 31 December 2018; doi:10.1038/s41589-018-0190-5A NO delivery system that depends on the hydrolysis of an alkyl-galactose-conjugated NO prodrug by an engineered galactosidase developed using a ‘bump-and-hole’ strategy enabled targeted delivery of NO to specific…

Continue Reading

Conducting the CTD orchestra

Posted on Dec 31st, 2018 - By Carlos Mario Genes Robles

Conducting the CTD orchestraConducting the CTD orchestra, Published online: 31 December 2018; doi:10.1038/s41589-018-0201-6The carboxyl-terminal domain (CTD) of RNA polymerase II (Pol II) is post-translationally modified during gene expression. A recent study has identified a CTD kinase, Hrr25, that regulates the termination of noncoding RNA genes by recruiting Rtt103, a key termination…

Continue Reading

Activation of silent biosynthetic gene clusters using transcription factor decoys

Posted on Dec 31st, 2018 - By Bin Wang

Activation of silent biosynthetic gene clusters using transcription factor decoysActivation of silent biosynthetic gene clusters using transcription factor decoys, Published online: 31 December 2018; doi:10.1038/s41589-018-0187-0Transcription factor decoys, DNA molecules designed to mimic regulatory DNAs and prevent repressors binding to their DNA targets, are used to achieve de-repression of silent biosynthetic gene clusters, resulting in production of new natural…

Continue Reading

Noncanonical CTD kinases regulate RNA polymerase II in a gene-class-specific manner

Posted on Dec 31st, 2018 - By Corey M. Nemec

Noncanonical CTD kinases regulate RNA polymerase II in a gene-class-specific mannerNoncanonical CTD kinases regulate RNA polymerase II in a gene-class-specific manner, Published online: 31 December 2018; doi:10.1038/s41589-018-0194-1Ten new RNA polymerase II kinases were identified, of these Hrr25 was engineered to enable covalent and noncovalent chemical inhibition in vivo, revealing that this kinase regulates polymerase function at noncoding snoRNA…

Continue Reading

Publisher Correction: Shared strategies for β-lactam catabolism in the soil microbiome

Posted on Dec 27th, 2018 - By Terence S. Crofts

Publisher Correction: Shared strategies for β-lactam catabolism in the soil microbiomePublisher Correction: Shared strategies for β-lactam catabolism in the soil microbiome, Published online: 27 December 2018; doi:10.1038/s41589-018-0208-zPublisher Correction: Shared strategies for β-lactam catabolism in the soil…

Continue Reading

Publisher Correction: Crystal structure of misoprostol bound to the labor inducer prostaglandin E<sub>2</sub> receptor

Posted on Dec 20th, 2018 - By Martin Audet

Publisher Correction: Crystal structure of misoprostol bound to the labor inducer prostaglandin E2 receptorPublisher Correction: Crystal structure of misoprostol bound to the labor inducer prostaglandin E<sub>2</sub> receptor, Published online: 20 December 2018; doi:10.1038/s41589-018-0214-1Publisher Correction: Crystal structure of misoprostol bound to the labor inducer prostaglandin E2…

Continue Reading

Metalloprotein switches that display chemical-dependent electron transfer in cells

Posted on Dec 17th, 2018 - By Joshua T. Atkinson

Metalloprotein switches that display chemical-dependent electron transfer in cellsMetalloprotein switches that display chemical-dependent electron transfer in cells, Published online: 17 December 2018; doi:10.1038/s41589-018-0192-3Designed split ferredoxins, fused to protein fragments that associate under certain conditions such as the presence of rapamycin, enable transcriptional and post-translational control over electron transfer in Escherichia coli cells and…

Continue Reading

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

Posted on Dec 17th, 2018 - By Boyuan Wang

Affinity-based capture and identification of protein effectors of the growth regulator ppGppAffinity-based capture and identification of protein effectors of the growth regulator ppGpp, Published online: 17 December 2018; doi:10.1038/s41589-018-0183-4A mass-spectrometry-based approach to identify E. coli targets of ppGpp finds 56 putative targets including enzymes involved in nucleotide synthesis, such as PurF, which is directly inhibited by ppGpp, regulating adenosine and guanine nucleotide…

Continue Reading

Structural basis of 7SK RNA 5′-γ-phosphate methylation and retention by MePCE

Posted on Dec 17th, 2018 - By Yuan Yang

Structural basis of 7SK RNA 5′-γ-phosphate methylation and retention by MePCEStructural basis of 7SK RNA 5′-γ-phosphate methylation and retention by MePCE, Published online: 17 December 2018; doi:10.1038/s41589-018-0188-zStructural analysis of the human MePCE methyltransferase domain in complex with 7SK in the presence of SAH or SAM reveals that MePCE has higher affinity for capped 7SK and holds it for subsequent assembly of 7SK…

Continue Reading

E2 enzymes: lessons in ubiquitin transfer from XLID patients

Posted on Dec 10th, 2018 - By Martina Foglizzo

E2 enzymes: lessons in ubiquitin transfer from XLID patientsE2 enzymes: lessons in ubiquitin transfer from XLID patients, Published online: 10 December 2018; doi:10.1038/s41589-018-0191-4Characterization of a novel mutation in the E2 ubiquitin-conjugating enzyme UBE2A accounts for the decreased activity of the mutant enzyme that underlies disease and provides important insight into the catalytic mechanism of…

Continue Reading

Mechanistic insights revealed by a UBE2A mutation linked to intellectual disability

Posted on Dec 10th, 2018 - By Juliana Ferreira de Oliveira

Mechanistic insights revealed by a UBE2A mutation linked to intellectual disabilityMechanistic insights revealed by a UBE2A mutation linked to intellectual disability, Published online: 10 December 2018; doi:10.1038/s41589-018-0177-2Structural and biochemical analysis of a UBE2A mutation linked to intellectual disability reveals that the Q93E mutant perturbs the E2 catalytic microenvironment essential for lysine deprotonation during the ubiquitin-transfer…

Continue Reading

<i>N</i><sup>6</sup>-mA condenses chromatin

Posted on Dec 10th, 2018 - By Yiyun Song

N6-mA condenses chromatin<i>N</i><sup>6</sup>-mA condenses chromatin, Published online: 10 December 2018; doi:10.1038/s41589-018-0199-9N6-mA condenses…

Continue Reading

Riboregulated toehold-gated gRNA for programmable CRISPR–Cas9 function

Posted on Dec 10th, 2018 - By Ka-Hei Siu

Riboregulated toehold-gated gRNA for programmable CRISPR–Cas9 functionRiboregulated toehold-gated gRNA for programmable CRISPR–Cas9 function, Published online: 10 December 2018; doi:10.1038/s41589-018-0186-1Engineering of toehold-gated guide RNA (thgRNA) by tethering toehold riboswitches to sgRNAs enables the activation of CRISPR–Cas9 genome editing or transcriptional regulation in response to complementary synthetic or endogenous cellular…

Continue Reading

The bacteria that move me

Posted on Dec 10th, 2018 - By Mirella Bucci

The bacteria that move meThe bacteria that move me, Published online: 10 December 2018; doi:10.1038/s41589-018-0198-xThe bacteria that move…

Continue Reading

<i>N</i><sup>6-</sup>Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation

Posted on Dec 10th, 2018 - By Honghui Ma

N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation<i>N</i><sup>6-</sup>Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation, Published online: 10 December 2018; doi:10.1038/s41589-018-0184-3ZCCHC4 was identified as a mammalian ribosome RNA (rRNA) N6-methyladenosine (m6A) writer protein that installs m6A 4220 in 28S rRNA. 28S rRNA methylation affects global translation and cell growth and contributes to tumorigenesis in…

Continue Reading

Design of fast proteolysis-based signaling and logic circuits in mammalian cells

Posted on Dec 10th, 2018 - By Tina Fink

Design of fast proteolysis-based signaling and logic circuits in mammalian cellsDesign of fast proteolysis-based signaling and logic circuits in mammalian cells, Published online: 10 December 2018; doi:10.1038/s41589-018-0181-6Protease-cleavable orthogonal-coiled-coil-based (SPOC) systems, in which split viral proteases are activated by small molecules and cleave coiled-coil protease substrates, reprogram signaling with rapid kinetics in mammalian…

Continue Reading

Lanthanide lover

Posted on Dec 10th, 2018 - By Caitlin Deane

Lanthanide loverLanthanide lover, Published online: 10 December 2018; doi:10.1038/s41589-018-0196-zLanthanide…

Continue Reading

Ligand binding to human prostaglandin E receptor EP<sub>4</sub> at the lipid-bilayer interface

Posted on Dec 3rd, 2018 - By Yosuke Toyoda

Ligand binding to human prostaglandin E receptor EP4 at the lipid-bilayer interfaceLigand binding to human prostaglandin E receptor EP<sub>4</sub> at the lipid-bilayer interface, Published online: 03 December 2018; doi:10.1038/s41589-018-0131-3The structure of human prostaglandin E receptor EP4 in complex with antagonist ONO-AE3-208 and a functional antibody reveals a ligand-binding site at the interface of the lipid bilayer that is unique among…

Continue Reading

Structural basis for ligand recognition of the human thromboxane A<sub>2</sub> receptor

Posted on Dec 3rd, 2018 - By Hengxin Fan

Structural basis for ligand recognition of the human thromboxane A2 receptorStructural basis for ligand recognition of the human thromboxane A<sub>2</sub> receptor, Published online: 03 December 2018; doi:10.1038/s41589-018-0170-9Structures of the human thromboxane A2 receptor, a member of the prostanoid family of G-protein-coupled receptors, in complex with two synthetic antagonists reveal that ligands access the ligand-binding pocket from the plane of the lipid…

Continue Reading

Crystal structure of the endogenous agonist-bound prostanoid receptor EP3

Posted on Dec 3rd, 2018 - By Kazushi Morimoto

Crystal structure of the endogenous agonist-bound prostanoid receptor EP3Crystal structure of the endogenous agonist-bound prostanoid receptor EP3, Published online: 03 December 2018; doi:10.1038/s41589-018-0171-8Structural analysis of prostaglandin E receptor EP3, a member of the prostanoid receptor subfamily of GPCRs, in complex with the endogenous agonist PGE2 reveals important interactions and motions required for receptor…

Continue Reading

Structures shed light on prostanoid signaling

Posted on Dec 3rd, 2018 - By Kaspar Hollenstein

Structures shed light on prostanoid signalingStructures shed light on prostanoid signaling, Published online: 03 December 2018; doi:10.1038/s41589-018-0178-1Prostanoids signal through G-protein-coupled receptors to regulate diverse physiological processes. Structures of three prostanoid receptors in inactive and active conformations now uncover the molecular determinants of ligand recognition and receptor activation and offer new opportunities for drug…

Continue Reading

Crystal structure of misoprostol bound to the labor inducer prostaglandin E<sub>2</sub> receptor

Posted on Dec 3rd, 2018 - By Martin Audet

Crystal structure of misoprostol bound to the labor inducer prostaglandin E2 receptorCrystal structure of misoprostol bound to the labor inducer prostaglandin E<sub>2</sub> receptor, Published online: 03 December 2018; doi:10.1038/s41589-018-0160-yA structure of the prostaglandin E2 receptor 3 (EP3) bound to the agonist misoprostol shows a completely enclosed binding pocket with a structured water molecule that coordinates misoprostol's ring structure and explains the receptor's…

Continue Reading

Programmable and printable <i>Bacillus subtilis</i> biofilms as engineered living materials

Posted on Dec 3rd, 2018 - By Jiaofang Huang

Programmable and printable Bacillus subtilis biofilms as engineered living materialsProgrammable and printable <i>Bacillus subtilis</i> biofilms as engineered living materials, Published online: 03 December 2018; doi:10.1038/s41589-018-0169-2Co-opting the amyloid machinery from Bacillus subtilis, engineering of TasA fusion proteins enables the assembly of functionalized biofilms with tunable physicochemical properties that are amenable to 3D printing and microencapsulation…

Continue Reading

Publisher Correction: Structural insights into binding specificity, efficacy and bias of a β<sub>2</sub>AR partial agonist

Posted on Nov 30th, 2018 - By Matthieu Masureel

Publisher Correction: Structural insights into binding specificity, efficacy and bias of a β2AR partial agonistPublisher Correction: Structural insights into binding specificity, efficacy and bias of a β<sub>2</sub>AR partial agonist, Published online: 30 November 2018; doi:10.1038/s41589-018-0182-5Publisher Correction: Structural insights into binding specificity, efficacy and bias of a β2AR partial…

Continue Reading

<i>Escherichia</i> coli “Marionette” strains with 12 highly optimized small-molecule sensors

Posted on Nov 26th, 2018 - By Adam J. Meyer

Escherichia coli “Marionette” strains with 12 highly optimized small-molecule sensors<i>Escherichia</i> coli “Marionette” strains with 12 highly optimized small-molecule sensors, Published online: 26 November 2018; doi:10.1038/s41589-018-0168-3A directed evolution approach was applied to optimize a set of 12 small-molecule-responsive biosensors, which led to the engineering of “Marionette” strains of Escherichia coli incorporating these sensors for biotechnological…

Continue Reading

Polarized displacement by transcription activator-like effectors for regulatory circuits

Posted on Nov 19th, 2018 - By Tina Lebar

Polarized displacement by transcription activator-like effectors for regulatory circuitsPolarized displacement by transcription activator-like effectors for regulatory circuits, Published online: 19 November 2018; doi:10.1038/s41589-018-0163-8The observation that transcription activator-like effectors (TALES) displace TALES bound at adjacent downstream DNA enables engineered regulation of gene expression, displacement of other DNA binding proteins and construction of logic-gated…

Continue Reading

Failure to convert

Posted on Nov 14th, 2018 - By Grant Miura

Failure to convertFailure to convert, Published online: 14 November 2018; doi:10.1038/s41589-018-0172-7Failure to…

Continue Reading

Identification of <i>Chaoborus</i> kairomone chemicals that induce defences in <i>Daphnia</i>

Posted on Nov 14th, 2018 - By Linda C. Weiss

Identification of Chaoborus kairomone chemicals that induce defences in DaphniaIdentification of <i>Chaoborus</i> kairomone chemicals that induce defences in <i>Daphnia</i>, Published online: 14 November 2018; doi:10.1038/s41589-018-0164-7The freshwater microcrustacean Daphnia pulex forms defensive neckteeth in response to a collection of chemical cues (the kairomone), now identified as certain fatty acids conjugated to glutamine, released during digestion by its…

Continue Reading

Metal Enterococcus equipment

Posted on Nov 14th, 2018 - By Mirella Bucci

Metal Enterococcus equipmentMetal Enterococcus equipment, Published online: 14 November 2018; doi:10.1038/s41589-018-0173-6Metal Enterococcus…

Continue Reading

Devilish diatoms

Posted on Nov 14th, 2018 - By Caitlin Deane

Devilish diatomsDevilish diatoms, Published online: 14 November 2018; doi:10.1038/s41589-018-0175-4Devilish…

Continue Reading

Transcriptional recorder

Posted on Nov 14th, 2018 - By Yiyun Song

Transcriptional recorderTranscriptional recorder, Published online: 14 November 2018; doi:10.1038/s41589-018-0174-5Transcriptional…

Continue Reading

Expanding the terpenoid kingdom

Posted on Nov 14th, 2018 - By Yongjin J. Zhou

Expanding the terpenoid kingdomExpanding the terpenoid kingdom, Published online: 14 November 2018; doi:10.1038/s41589-018-0167-4Terpenoids are assembled from five-carbon (C5) units, which limits the available scaffold chemical space for the discovery of bioactive molecules. A combination of enzyme and metabolic engineering now enables biosynthesis of a plethora of non-natural C11…

Continue Reading

Disrupting the CD95–PLCγ1 interaction prevents Th17-driven inflammation

Posted on Nov 14th, 2018 - By Amanda Poissonnier

Disrupting the CD95–PLCγ1 interaction prevents Th17-driven inflammationDisrupting the CD95–PLCγ1 interaction prevents Th17-driven inflammation, Published online: 14 November 2018; doi:10.1038/s41589-018-0162-9The HIV protease inhibitor ritonavir targets the calcium-inducing domain (CID) of CD95 to block interactions with PLCγ1. Peptidomimetics targeting the CD95 CID prevents accumulation of inflammatory Th17 cells observed in systemic lupus…

Continue Reading

Synthesis of 11-carbon terpenoids in yeast using protein and metabolic engineering

Posted on Nov 14th, 2018 - By Codruta Ignea

Synthesis of 11-carbon terpenoids in yeast using protein and metabolic engineeringSynthesis of 11-carbon terpenoids in yeast using protein and metabolic engineering, Published online: 14 November 2018; doi:10.1038/s41589-018-0166-5Yeast engineered to produce the six-carbon terpene building block 2-methyl-geranyl diphosphate, coupled with terpene synthases engineered to accept this noncanonical substrate, enables the biosynthesis of a collection of new C11 terpenoid…

Continue Reading

HIP1R targets PD-L1 to lysosomal degradation to alter T cell–mediated cytotoxicity

Posted on Nov 5th, 2018 - By Huanbin Wang

HIP1R targets PD-L1 to lysosomal degradation to alter T cell–mediated cytotoxicityHIP1R targets PD-L1 to lysosomal degradation to alter T cell–mediated cytotoxicity, Published online: 05 November 2018; doi:10.1038/s41589-018-0161-xHIP1R directly interacts with PD-L1 and targets PD-L1 for lysosomal degradation. Development of a rationally designed peptide incorporating the PD-L1 binding sequence of HIP1R with a lysosomal targeting sequence promotes PD-L1…

Continue Reading

The multicatalytic compartment of propionyl-CoA synthase sequesters a toxic metabolite

Posted on Oct 29th, 2018 - By Iria Bernhardsgrütter

The multicatalytic compartment of propionyl-CoA synthase sequesters a toxic metaboliteThe multicatalytic compartment of propionyl-CoA synthase sequesters a toxic metabolite, Published online: 29 October 2018; doi:10.1038/s41589-018-0153-xStructural and biochemical analysis of propionyl-CoA synthase reveals that it forms a reaction chamber containing three active sites, which sequesters the reactive intermediate acrylyl-CoA during the conversion of 3-hydroxypropionate to…

Continue Reading

Structure-guided development of YEATS domain inhibitors by targeting π-π-π stacking

Posted on Oct 29th, 2018 - By Xin Li

Structure-guided development of YEATS domain inhibitors by targeting π-π-π stackingStructure-guided development of YEATS domain inhibitors by targeting π-π-π stacking, Published online: 29 October 2018; doi:10.1038/s41589-018-0144-yAn inhibitor of the YEATS domain was developed by targeting a unique π-π-π stacking in the YEATS–Kcr recognition. An ENL YEATS-selective inhibitor, XL-13m, helps probe the YEATS-dependent role of ENL in the leukemogenic transcription…

Continue Reading

Identification of a cellularly active SIRT6 allosteric activator

Posted on Oct 29th, 2018 - By Zhimin Huang

Identification of a cellularly active SIRT6 allosteric activatorIdentification of a cellularly active SIRT6 allosteric activator, Published online: 29 October 2018; doi:10.1038/s41589-018-0150-0The use of an allosteric drug-design method resulted in the identification of a first-in-class cellularly active SIRT6 activator that induces cell-cycle arrest in the G0–G1 phase, thus suppressing proliferation in human hepatocellular carcinoma…

Continue Reading

Chaperoning partners

Posted on Oct 16th, 2018 - By Grant Miura

Chaperoning partnersChaperoning partners, Published online: 16 October 2018; doi:10.1038/s41589-018-0157-6Chaperoning…

Continue Reading

Enzyme promiscuity drives branched-chain fatty acid synthesis in adipose tissues

Posted on Oct 16th, 2018 - By Martina Wallace

Enzyme promiscuity drives branched-chain fatty acid synthesis in adipose tissuesEnzyme promiscuity drives branched-chain fatty acid synthesis in adipose tissues, Published online: 16 October 2018; doi:10.1038/s41589-018-0132-2mmBCFAs are endogenous fatty acids synthesized from BCAAs by brown and white adipose tissue via CrAT and FASN promiscuity. BCAA catabolism and mmBCFA lipogenesis are decreased by obesity-induced adipose hypoxia and influenced by the…

Continue Reading

No more ESKAPE

Posted on Oct 16th, 2018 - By Mirella Bucci

No more ESKAPENo more ESKAPE, Published online: 16 October 2018; doi:10.1038/s41589-018-0156-7No more…

Continue Reading

Small-molecule-based regulation of RNA-delivered circuits in mammalian cells

Posted on Oct 16th, 2018 - By Tyler E. Wagner

Small-molecule-based regulation of RNA-delivered circuits in mammalian cellsSmall-molecule-based regulation of RNA-delivered circuits in mammalian cells, Published online: 16 October 2018; doi:10.1038/s41589-018-0146-9Engineering of small-molecule-responsive RNA-binding proteins enables chemical regulation of modified mRNA or RNA replicon expression within mammalian cells for applications in synthetic circuit design and RNA-centered…

Continue Reading

Trading on thionoesters

Posted on Oct 16th, 2018 - By Caitlin Deane

Trading on thionoestersTrading on thionoesters, Published online: 16 October 2018; doi:10.1038/s41589-018-0158-5Trading on…

Continue Reading

Structural insights into binding specificity, efficacy and bias of a β<sub>2</sub>AR partial agonist

Posted on Oct 16th, 2018 - By Matthieu Masureel

Structural insights into binding specificity, efficacy and bias of a β2AR partial agonistStructural insights into binding specificity, efficacy and bias of a β<sub>2</sub>AR partial agonist, Published online: 16 October 2018; doi:10.1038/s41589-018-0145-xThe active-state structure of a GPCR occupied by a partial agonist, β2AR with salmeterol, together with mutagenesis and biophysical studies, explains this ligand's unusual pharmacological…

Continue Reading

A new spot for PKR

Posted on Oct 16th, 2018 - By Yiyun Song

A new spot for PKRA new spot for PKR, Published online: 16 October 2018; doi:10.1038/s41589-018-0159-4A new spot for…

Continue Reading

Metabolic repair through emergence of new pathways in <i>Escherichia coli</i>

Posted on Oct 16th, 2018 - By Sammy Pontrelli

Metabolic repair through emergence of new pathways in Escherichia coliMetabolic repair through emergence of new pathways in <i>Escherichia coli</i>, Published online: 16 October 2018; doi:10.1038/s41589-018-0149-6In response to the deletion of key genes involved in biosynthesis of the essential CoA precursor β-alanine, Escherichia coli overcomes this pathway damage by successively evolving alternative metabolic…

Continue Reading

Compartmentalizing acid stress in bacteria

Posted on Oct 15th, 2018 - By Colin Kleanthous

Compartmentalizing acid stress in bacteriaCompartmentalizing acid stress in bacteria, Published online: 15 October 2018; doi:10.1038/s41589-018-0148-7A Donnan equilibrium causes an influx of chloride ions into the Escherichia coli periplasm when the bacterium finds itself in gastric fluid. The combination of low pH and high anion concentration drives proteins to aggregate, a potentially lethal event unless prevented by specific…

Continue Reading

In vivo chloride concentrations surge to proteotoxic levels during acid stress

Posted on Oct 15th, 2018 - By Frederick Stull

In vivo chloride concentrations surge to proteotoxic levels during acid stressIn vivo chloride concentrations surge to proteotoxic levels during acid stress, Published online: 15 October 2018; doi:10.1038/s41589-018-0143-zProtonation of periplasmic protein carboxylic groups creates a Donnan equilibrium in the bacterial periplasmic space at low pH, leading to accumulation of Cl− and unfolding and aggregation of periplasmic proteins, which can be rescued by…

Continue Reading

The splice is right

Posted on Oct 15th, 2018 - By James Palacino

The splice is rightThe splice is right, Published online: 15 October 2018; doi:10.1038/s41589-018-0147-8Current drug discovery efforts focus on proteins because of their ability to form stable, structured pockets. A recent study demonstrates that targeting stable, structured bioactive RNA motifs, such as autocatalytic introns, may provide a novel method of expanding druggability and…

Continue Reading

Small molecules that target group II introns are potent antifungal agents

Posted on Oct 15th, 2018 - By Olga Fedorova

Small molecules that target group II introns are potent antifungal agentsSmall molecules that target group II introns are potent antifungal agents, Published online: 15 October 2018; doi:10.1038/s41589-018-0142-0High-throughput screening followed by an examination of structure–activity relationship-based optimization resulted in the identification of potent small-molecule inhibitors of group IIB intron splicing in fungal…

Continue Reading

New tricks for an old drug

Posted on Oct 8th, 2018 - By Barbara S. Nelson

New tricks for an old drugNew tricks for an old drug, Published online: 08 October 2018; doi:10.1038/s41589-018-0137-xThe prodrug dimethyloxalylglycine (DMOG) is a well-known tool compound used to study hypoxia. New findings reveal that DMOG also inhibits glutamine metabolism and can be exploited to selectively kill some cancer cells, highlighting important caveats when using DMOG for hypoxia…

Continue Reading

MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG

Posted on Oct 8th, 2018 - By Louise Fets

MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOGMCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG, Published online: 08 October 2018; doi:10.1038/s41589-018-0136-yHigh intracellular concentrations of the α-ketoglutarate analog N-oxalylglycine, owing to MCT2-mediated transport of its newly described prodrug MOG, inhibit multiple enzymes in glutamine metabolism and selectively kill MCT2-expressing cancer…

Continue Reading

A new target for thalidomide

Posted on Sep 17th, 2018 - By Peter G. Wells

A new target for thalidomideA new target for thalidomide, Published online: 17 September 2018; doi:10.1038/s41589-018-0134-0One mechanism of thalidomide teratogenicity involves binding to the CUL4–CRBN E3 ubiquitin ligase complex, which then mediates the degradation of transcription factors. New studies reveal that species-specific variants of the transcription factor SALL4 are differentially ubiquitinated and degraded via the thalidomide-bound…

Continue Reading

Cost–benefit analysis

Posted on Sep 17th, 2018 - By Grant Miura

Cost–benefit analysisCost–benefit analysis, Published online: 17 September 2018; doi:10.1038/s41589-018-0139-8Cost–benefit…

Continue Reading