2,728 results match your criteria Nature Chemical Biology [Journal]


Chemogenetics defines receptor-mediated functions of short chain free fatty acids.

Nat Chem Biol 2019 May 15;15(5):489-498. Epub 2019 Apr 15.

Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

Differentiating actions of short chain fatty acids (SCFAs) at free fatty acid receptor 2 (FFA2) from other free fatty acid-responsive receptors and from non-receptor-mediated effects has been challenging. Using a novel chemogenetic and knock-in strategy, whereby an engineered variant of FFA2 (FFA2-DREADD) that is unresponsive to natural SCFAs but is instead activated by sorbic acid replaced the wild-type receptor, we determined that activation of FFA2 in differentiated adipocytes and colonic crypt enteroendocrine cells of mouse accounts fully for SCFA-regulated lipolysis and release of the incretin glucagon-like peptide-1 (GLP-1), respectively. In vivo studies confirmed the specific role of FFA2 in GLP-1 release and also demonstrated a direct role for FFA2 in accelerating gut transit. Read More

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http://www.nature.com/articles/s41589-019-0270-1
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http://dx.doi.org/10.1038/s41589-019-0270-1DOI Listing
May 2019
2 Reads

CRISPR-suppressor scanning reveals a nonenzymatic role of LSD1 in AML.

Nat Chem Biol 2019 May 15;15(5):529-539. Epub 2019 Apr 15.

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.

Understanding the mechanism of small molecules is a critical challenge in chemical biology and drug discovery. Medicinal chemistry is essential for elucidating drug mechanism, enabling variation of small molecule structure to gain structure-activity relationships (SARs). However, the development of complementary approaches that systematically vary target protein structure could provide equally informative SARs for investigating drug mechanism and protein function. Read More

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http://dx.doi.org/10.1038/s41589-019-0263-0DOI Listing
May 2019
1 Read

Under pressure.

Authors:
Grant Miura

Nat Chem Biol 2019 May;15(5):427

Nature Chemical Biology, .

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http://dx.doi.org/10.1038/s41589-019-0282-xDOI Listing

Marking histones.

Authors:
Yiyun Song

Nat Chem Biol 2019 May;15(5):427

Nature Chemical Biology, .

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http://dx.doi.org/10.1038/s41589-019-0283-9DOI Listing

Cannabinoids on the rise.

Authors:
Caitlin Deane

Nat Chem Biol 2019 May;15(5):427

Nature Chemical Biology, .

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http://dx.doi.org/10.1038/s41589-019-0280-zDOI Listing

Avoiding the dumpster.

Authors:
Grant Miura

Nat Chem Biol 2019 May;15(5):427

Nature Chemical Biology, .

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http://dx.doi.org/10.1038/s41589-019-0281-yDOI Listing

Dynamic assembly of protein disulfide isomerase in catalysis of oxidative folding.

Nat Chem Biol 2019 May 15;15(5):499-509. Epub 2019 Apr 15.

Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan.

Time-resolved direct observations of proteins in action provide essential mechanistic insights into biological processes. Here, we present mechanisms of action of protein disulfide isomerase (PDI)-the most versatile disulfide-introducing enzyme in the endoplasmic reticulum-during the catalysis of oxidative protein folding. Single-molecule analysis by high-speed atomic force microscopy revealed that oxidized PDI is in rapid equilibrium between open and closed conformations, whereas reduced PDI is maintained in the closed state. Read More

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http://www.nature.com/articles/s41589-019-0268-8
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May 2019
6 Reads

Structure and functional reselection of the Mango-III fluorogenic RNA aptamer.

Nat Chem Biol 2019 May 15;15(5):472-479. Epub 2019 Apr 15.

Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.

Several turn-on RNA aptamers that activate small-molecule fluorophores have been selected in vitro. Among these, the ~30 nucleotide Mango-III is notable because it binds the thiazole orange derivative TO1-Biotin with high affinity and fluoresces brightly (quantum yield 0.55). Read More

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http://dx.doi.org/10.1038/s41589-019-0267-9DOI Listing

Scaffold and organism hopping with chemical probes.

Authors:
Jürg Gertsch

Nat Chem Biol 2019 May;15(5):428-429

Institute of Biochemistry and Molecular Medicine, NCCR TransCure, University of Bern, Bern, Switzerland.

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http://dx.doi.org/10.1038/s41589-019-0275-9DOI Listing

Bromodomain inhibition of the coactivators CBP/EP300 facilitate cellular reprogramming.

Nat Chem Biol 2019 May 8;15(5):519-528. Epub 2019 Apr 8.

School of Medicine, Koç University, Istanbul, Turkey.

Silencing of the somatic cell type-specific genes is a critical yet poorly understood step in reprogramming. To uncover pathways that maintain cell identity, we performed a reprogramming screen using inhibitors of chromatin factors. Here, we identify acetyl-lysine competitive inhibitors targeting the bromodomains of coactivators CREB (cyclic-AMP response element binding protein) binding protein (CBP) and E1A binding protein of 300 kDa (EP300) as potent enhancers of reprogramming. Read More

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http://www.nature.com/articles/s41589-019-0264-z
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May 2019
8 Reads

Structure of McsB, a protein kinase for regulated arginine phosphorylation.

Nat Chem Biol 2019 May 8;15(5):510-518. Epub 2019 Apr 8.

Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.

Protein phosphorylation regulates key processes in all organisms. In Gram-positive bacteria, protein arginine phosphorylation plays a central role in protein quality control by regulating transcription factors and marking aberrant proteins for degradation. Here, we report structural, biochemical, and in vivo data of the responsible kinase, McsB, the founding member of an arginine-specific class of protein kinases. Read More

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http://www.nature.com/articles/s41589-019-0265-y
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May 2019
4 Reads

ARGuing for a new kinase class.

Authors:
Titus J Boggon

Nat Chem Biol 2019 May;15(5):431-432

Department of Pharmacology and Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.

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http://dx.doi.org/10.1038/s41589-019-0272-zDOI Listing
May 2019
1 Read

Author Correction: tRNA tracking for direct measurements of protein synthesis kinetics in live cells.

Nat Chem Biol 2019 Apr 5. Epub 2019 Apr 5.

Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.

In the version of this article originally published, the values on the y axis of Fig. 6d were incorrect. They should be 0. Read More

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http://www.nature.com/articles/s41589-019-0266-x
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http://dx.doi.org/10.1038/s41589-019-0266-xDOI Listing
April 2019
2 Reads

Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides.

Nat Chem Biol 2019 May 1;15(5):463-471. Epub 2019 Apr 1.

Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA.

Cell wall glycopolymers on the surface of Gram-positive bacteria are fundamental to bacterial physiology and infection biology. Here we identify gacH, a gene in the Streptococcus pyogenes group A carbohydrate (GAC) biosynthetic cluster, in two independent transposon library screens for its ability to confer resistance to zinc and susceptibility to the bactericidal enzyme human group IIA-secreted phospholipase A. Subsequent structural and phylogenetic analysis of the GacH extracellular domain revealed that GacH represents an alternative class of glycerol phosphate transferase. Read More

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http://dx.doi.org/10.1038/s41589-019-0251-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470023PMC

An orange calcium-modulated bioluminescent indicator for non-invasive activity imaging.

Nat Chem Biol 2019 May 1;15(5):433-436. Epub 2019 Apr 1.

Department of Neurobiology, Stanford University, Stanford, CA, USA.

Fluorescent indicators are used widely to visualize calcium dynamics downstream of membrane depolarization or G-protein-coupled receptor activation, but are poorly suited for non-invasive imaging in mammals. Here, we report a bright calcium-modulated bioluminescent indicator named Orange CaMBI (Orange Calcium-modulated Bioluminescent Indicator). Orange CaMBI reports calcium dynamics in single cells and, in the context of a transgenic mouse, reveals calcium oscillations in whole organs in an entirely non-invasive manner. Read More

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http://www.nature.com/articles/s41589-019-0256-z
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http://dx.doi.org/10.1038/s41589-019-0256-zDOI Listing
May 2019
1 Read

Analysis of modular bioengineered antimicrobial lanthipeptides at nanoliter scale.

Nat Chem Biol 2019 May 1;15(5):437-443. Epub 2019 Apr 1.

Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.

The rise of antibiotic resistance demands the acceleration of molecular diversification strategies to inspire new chemical entities for antibiotic medicines. We report here on the large-scale engineering of ribosomally synthesized and post-translationally modified antimicrobial peptides carrying the ring-forming amino acid lanthionine. New-to-nature variants featuring distinct properties were obtained by combinatorial shuffling of peptide modules derived from 12 natural antimicrobial lanthipeptides and processing by a promiscuous post-translational modification machinery. Read More

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http://dx.doi.org/10.1038/s41589-019-0250-5DOI Listing

Cascaded amplifying circuits enable ultrasensitive cellular sensors for toxic metals.

Nat Chem Biol 2019 May 25;15(5):540-548. Epub 2019 Mar 25.

School of Biological Sciences, University of Edinburgh, Edinburgh, UK.

Cell-based biosensors have great potential to detect various toxic and pathogenic contaminants in aqueous environments. However, frequently they cannot meet practical requirements due to insufficient sensing performance. To address this issue, we investigated a modular, cascaded signal amplifying methodology. Read More

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http://dx.doi.org/10.1038/s41589-019-0244-3DOI Listing
May 2019
1 Read

Pharmacological convergence reveals a lipid pathway that regulates C. elegans lifespan.

Nat Chem Biol 2019 May 25;15(5):453-462. Epub 2019 Mar 25.

The Skaggs Institute for Chemical Biology, Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.

Phenotypic screening has identified small-molecule modulators of aging, but the mechanism of compound action often remains opaque due to the complexities of mapping protein targets in whole organisms. Here, we combine a library of covalent inhibitors with activity-based protein profiling to coordinately discover bioactive compounds and protein targets that extend lifespan in Caenorhabditis elegans. We identify JZL184-an inhibitor of the mammalian endocannabinoid (eCB) hydrolase monoacylglycerol lipase (MAGL or MGLL)-as a potent inducer of longevity, a result that was initially perplexing as C. Read More

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http://www.nature.com/articles/s41589-019-0243-4
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May 2019
14 Reads

Molybdenum cofactor transfer from bacteria to nematode mediates sulfite detoxification.

Nat Chem Biol 2019 May 25;15(5):480-488. Epub 2019 Mar 25.

Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.

The kingdoms of life share many small molecule cofactors and coenzymes. Molybdenum cofactor (Moco) is synthesized by many archaea, bacteria, and eukaryotes, and is essential for human development. The genome of Caenorhabditis elegans contains all of the Moco biosynthesis genes, and surprisingly these genes are not essential if the animals are fed a bacterial diet that synthesizes Moco. Read More

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http://www.nature.com/articles/s41589-019-0249-y
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http://dx.doi.org/10.1038/s41589-019-0249-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470025PMC
May 2019
10 Reads

Harvesting Moco.

Nat Chem Biol 2019 May;15(5):429-430

Department of Plant Biology, Braunschweig University of Technology, Braunschweig, Germany.

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http://dx.doi.org/10.1038/s41589-019-0257-yDOI Listing

Dual phenazine gene clusters enable diversification during biosynthesis.

Nat Chem Biol 2019 04 18;15(4):331-339. Epub 2019 Mar 18.

Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, Frankfurt am Main, Germany.

Biosynthetic gene clusters (BGCs) bridging genotype and phenotype continuously evolve through gene mutations and recombinations to generate chemical diversity. Phenazine BGCs are widespread in bacteria, and the biosynthetic mechanisms of the formation of the phenazine structural core have been illuminated in the last decade. However, little is known about the complex phenazine core-modification machinery. Read More

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http://dx.doi.org/10.1038/s41589-019-0246-1DOI Listing

Affinity selection and sequencing.

Authors:
Kit S Lam

Nat Chem Biol 2019 04;15(4):320-321

Department of Biochemistry and Molecular Medicine, Division of Hematology & Oncology, School of Medicine, UC Davis NCI-designated Comprehensive Cancer Center, University of California Davis, Sacramento, CA, USA.

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http://dx.doi.org/10.1038/s41589-019-0253-2DOI Listing

In-solution enrichment identifies peptide inhibitors of protein-protein interactions.

Nat Chem Biol 2019 04 18;15(4):410-418. Epub 2019 Mar 18.

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.

The use of competitive inhibitors to disrupt protein-protein interactions (PPIs) holds great promise for the treatment of disease. However, the discovery of high-affinity inhibitors can be a challenge. Here we report a platform for improving the affinity of peptide-based PPI inhibitors using non-canonical amino acids. Read More

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http://dx.doi.org/10.1038/s41589-019-0245-2DOI Listing
April 2019
2 Reads

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

Nat Chem Biol 2019 04 18;15(4):384-390. Epub 2019 Mar 18.

Department of Biological Sciences, University of Calgary, Calgary, AB, Canada.

The isomerization of neopinone to codeinone is a critical step in the biosynthesis of opiate alkaloids in opium poppy. Previously assumed to be spontaneous, the process is in fact catalyzed enzymatically by neopinone isomerase (NISO). Without NISO the primary metabolic products in the plant, in engineered microbes and in vitro are neopine and neomorphine, which are structural isomers of codeine and morphine, respectively. Read More

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http://dx.doi.org/10.1038/s41589-019-0247-0DOI Listing
April 2019
1 Read

An appetite for aromatics.

Authors:
Mirella Bucci

Nat Chem Biol 2019 04;15(4):315

Nature Chemical Biology, .

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http://dx.doi.org/10.1038/s41589-019-0260-3DOI Listing
April 2019
1 Read

A new CRISPR scissor.

Authors:
Yiyun Song

Nat Chem Biol 2019 04;15(4):315

Nature Chemical Biology, .

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http://dx.doi.org/10.1038/s41589-019-0261-2DOI Listing

A broken heart can mend.

Authors:
Grant Miura

Nat Chem Biol 2019 04;15(4):315

Nature Chemical Biology, .

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http://www.nature.com/articles/s41589-019-0259-9
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April 2019
5 Reads

A better binder builder.

Authors:
Caitlin Deane

Nat Chem Biol 2019 04;15(4):315

Nature Chemical Biology, .

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http://www.nature.com/articles/s41589-019-0258-x
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April 2019
3 Reads

New roles for old RNA cap flavors.

Nat Chem Biol 2019 04;15(4):317-318

Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.

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http://dx.doi.org/10.1038/s41589-019-0252-3DOI Listing

Publisher Correction: Side chain determinants of biopolymer function during selection and replication.

Nat Chem Biol 2019 May;15(5):550

Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

In the version of this article originally published, several data points in Fig. 4c were shifted out of place during production. The corrected version of Fig. Read More

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http://dx.doi.org/10.1038/s41589-019-0254-1DOI Listing
May 2019
12.996 Impact Factor

A fluorogenic array for temporally unlimited single-molecule tracking.

Nat Chem Biol 2019 04 11;15(4):401-409. Epub 2019 Mar 11.

Bioengineering, Stanford University, Stanford, CA, USA.

We describe three optical tags, ArrayG, ArrayD and ArrayG/N, for intracellular tracking of single molecules over milliseconds to hours. ArrayG is a fluorogenic tag composed of a green fluorescent protein-nanobody array and monomeric wild-type green fluorescent protein binders that are initially dim but brighten ~26-fold on binding with the array. By balancing the rates of binder production, photobleaching and stochastic binder exchange, we achieve temporally unlimited tracking of single molecules. Read More

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http://www.nature.com/articles/s41589-019-0241-6
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April 2019
2 Reads

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

Nat Chem Biol 2019 Mar 6. Epub 2019 Mar 6.

Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNCEshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

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http://dx.doi.org/10.1038/s41589-019-0242-5DOI Listing

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

Nat Chem Biol 2019 May;15(5):549

Laboratoire de Biologie et Pharmacologie Appliquée, Ecole normale supérieure Paris-Saclay, Cachan, France.

In the version of this article originally published, several co-authors had incorrect affiliation footnote numbers listed in the author list. Tatiana Cañeque and Angelica Mariani should each have affiliation numbers 3, 4 and 5, and Emmanuelle Charafe-Jauffret should have number 6. Additionally, there was an extra space in the name of co-author Robert P. Read More

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http://www.nature.com/articles/s41589-019-0255-0
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May 2019
14 Reads

Potassium channel selectivity filter dynamics revealed by single-molecule FRET.

Nat Chem Biol 2019 04 4;15(4):377-383. Epub 2019 Mar 4.

Center for Investigation of Membrane Excitability Diseases, Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.

Potassium (K) channels exhibit exquisite selectivity for conduction of K ions over other cations, particularly Na. High-resolution structures reveal an archetypal selectivity filter (SF) conformation in which dehydrated K ions, but not Na ions, are perfectly coordinated. Using single-molecule FRET (smFRET), we show that the SF-forming loop (SF-loop) in KirBac1. Read More

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http://www.nature.com/articles/s41589-019-0240-7
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http://dx.doi.org/10.1038/s41589-019-0240-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430689PMC
April 2019
9 Reads

A flexible filter maintains a tight grip.

Authors:
Adrian Gross

Nat Chem Biol 2019 04;15(4):319-320

Department of Biochemistry and Molecular Biology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.

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http://dx.doi.org/10.1038/s41589-019-0248-zDOI Listing
April 2019
1 Read

Bidirectional modulation of HIF-2 activity through chemical ligands.

Nat Chem Biol 2019 04 25;15(4):367-376. Epub 2019 Feb 25.

Integrative Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USA.

Hypoxia-inducible factor-2 (HIF-2) is a heterodimeric transcription factor formed through dimerization between an oxygen-sensitive HIF-2α subunit and its obligate partner subunit ARNT. Enhanced HIF-2 activity drives some cancers, whereas reduced activity causes anemia in chronic kidney disease. Therefore, modulation of HIF-2 activity via direct-binding ligands could provide many new therapeutic benefits. Read More

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http://dx.doi.org/10.1038/s41589-019-0234-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447045PMC
April 2019
4 Reads

FTO controls reversible mAm RNA methylation during snRNA biogenesis.

Nat Chem Biol 2019 04 18;15(4):340-347. Epub 2019 Feb 18.

Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA.

Small nuclear RNAs (snRNAs) are core spliceosome components and mediate pre-mRNA splicing. Here we show that snRNAs contain a regulated and reversible nucleotide modification causing them to exist as two different methyl isoforms, m and m, reflecting the methylation state of the adenosine adjacent to the snRNA cap. We find that snRNA biogenesis involves the formation of an initial m isoform with a single-methylated adenosine (2'-O-methyladenosine, Am), which is then converted to a dimethylated m isoform (N,2'-O-dimethyladenosine, mAm). Read More

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http://dx.doi.org/10.1038/s41589-019-0231-8DOI Listing

Tightening a deadly pore former.

Authors:
Jialing Lin

Nat Chem Biol 2019 04;15(4):316-317

Department of Biochemistry and Molecular Biology, and Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

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http://dx.doi.org/10.1038/s41589-019-0235-4DOI Listing

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

Nat Chem Biol 2019 May 18;15(5):444-452. Epub 2019 Feb 18.

Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, NY, USA.

Spastin is a microtubule-severing AAA (ATPases associated with diverse cellular activities) protein needed for cell division and intracellular vesicle transport. Currently, we lack chemical inhibitors to probe spastin function in such dynamic cellular processes. To design a chemical inhibitor of spastin, we tested selected heterocyclic scaffolds against wild-type protein and constructs with engineered mutations in the nucleotide-binding site that do not substantially disrupt ATPase activity. Read More

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http://dx.doi.org/10.1038/s41589-019-0225-6DOI Listing

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

Nat Chem Biol 2019 03 15;15(3):276-284. Epub 2019 Feb 15.

Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Lab for Synthetic Biochemistry, Technical University of Munich, Institute for Advanced Study, TUM-IAS, Garching, Germany.

Post-translational modification of proteins with ubiquitin and ubiquitin-like proteins (Ubls) is central to the regulation of eukaryotic cellular processes. Our ability to study the effects of ubiquitylation, however, is limited by the difficulty to prepare homogenously modified proteins in vitro and by the impossibility to selectively trigger specific ubiquitylation events in living cells. Here we combine genetic-code expansion, bioorthogonal Staudinger reduction and sortase-mediated transpeptidation to develop a general tool to ubiquitylate proteins in an inducible fashion. Read More

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http://dx.doi.org/10.1038/s41589-019-0227-4DOI Listing
March 2019
1 Read
12.996 Impact Factor

HIV seals an envelope.

Authors:
Mirella Bucci

Nat Chem Biol 2019 03;15(3):207

Nature Chemical Biology, .

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http://dx.doi.org/10.1038/s41589-019-0238-1DOI Listing

To be or not to be?

Authors:
Yiyun Song

Nat Chem Biol 2019 03;15(3):207

Nature Chemical Biology, .

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http://dx.doi.org/10.1038/s41589-019-0239-0DOI Listing

A super-powered S-layer.

Authors:
Caitlin Deane

Nat Chem Biol 2019 03;15(3):207

Nature Chemical Biology, .

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http://dx.doi.org/10.1038/s41589-019-0236-3DOI Listing

METTLing with translation.

Authors:
Grant Miura

Nat Chem Biol 2019 03;15(3):207

Nature Chemical Biology, .

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http://dx.doi.org/10.1038/s41589-019-0237-2DOI Listing

Decoding without the cipher.

Nat Chem Biol 2019 03;15(3):210-212

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

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http://dx.doi.org/10.1038/s41589-019-0230-9DOI Listing

Snappy cell division in Actinobacteria.

Authors:
Martin S Pavelka

Nat Chem Biol 2019 03;15(3):208-209

Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.

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http://dx.doi.org/10.1038/s41589-019-0226-5DOI Listing

Side chain determinants of biopolymer function during selection and replication.

Nat Chem Biol 2019 04 11;15(4):419-426. Epub 2019 Feb 11.

Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

The chemical functionalities within biopolymers determine their physical properties and biological activities. The relationship between the side chains available to a biopolymer population and the potential functions of the resulting polymers, however, has proven difficult to study experimentally. Using seven sets of chemically diverse charged, polar, and nonpolar side chains, we performed cycles of artificial translation, in vitro selections for binding to either PCSK9 or IL-6 protein, and replication on libraries of random side chain-functionalized nucleic acid polymers. Read More

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http://dx.doi.org/10.1038/s41589-019-0229-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430648PMC
April 2019
12.996 Impact Factor

PH-domain-binding inhibitors of nucleotide exchange factor BRAG2 disrupt Arf GTPase signaling.

Nat Chem Biol 2019 04 11;15(4):358-366. Epub 2019 Feb 11.

Laboratoire de Biologie et Pharmacologie Appliquée, Ecole normale supérieure Paris-Saclay, Cachan, France.

Peripheral membrane proteins orchestrate many physiological and pathological processes, making regulation of their activities by small molecules highly desirable. However, they are often refractory to classical competitive inhibition. Here, we demonstrate that potent and selective inhibition of peripheral membrane proteins can be achieved by small molecules that target protein-membrane interactions by a noncompetitive mechanism. Read More

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http://dx.doi.org/10.1038/s41589-019-0228-3DOI Listing
April 2019
18 Reads

Publisher Correction: N-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation.

Nat Chem Biol 2019 May;15(5):549

Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA.

In the version of this article originally published, the references were incorrectly re-ordered during production. The hyphen in "N-methyladenosine" in the title was also superscript. The errors have been corrected in the HTML and PDF versions of the paper. Read More

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http://dx.doi.org/10.1038/s41589-019-0233-6DOI Listing
May 2019
5 Reads

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

Nat Chem Biol 2019 May;15(5):549

Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, Republic of Korea.

In the version of this article originally published, reference to another structure of GenB1 was omitted (Dow, G. T., Thoden, J. Read More

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http://dx.doi.org/10.1038/s41589-019-0232-7DOI Listing
May 2019
5 Reads
12.996 Impact Factor