journal
MENU ▼
Read by QxMD icon Read
search

Nature Chemical Biology

journal
https://www.readbyqxmd.com/read/28628097/cpf1-proteins-excise-crispr-rnas-from-mrna-transcripts-in-mammalian-cells
#1
Guocai Zhong, Haimin Wang, Yujun Li, Mai H Tran, Michael Farzan
Cpf1 is a CRISPR effector protein that has greater specificity than Streptococcus pyogenes Cas9 (SpCas9) in genome-editing applications. Here we show that Lachnospiraceae bacterium (Lb) and Acidaminococus sp. (As) Cpf1 orthologs have RNase activities that can excise multiple CRISPR RNAs (crRNAs) from a single RNA polymerase II-driven RNA transcript expressed in mammalian cells. This property simplifies modification of multiple genomic targets and can be used to increase the efficiency of Cpf1-mediated editing...
June 19, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28628096/nucleation-and-growth-of-a-bacterial-functional-amyloid-at-single-fiber-resolution
#2
Mike Sleutel, Imke Van den Broeck, Nani Van Gerven, Cécile Feuillie, Wim Jonckheere, Claire Valotteau, Yves F Dufrêne, Han Remaut
Curli are functional amyloids produced by proteobacteria like Escherichia coli as part of the extracellular matrix that holds cells together into biofilms. The molecular events that occur during curli nucleation and fiber extension remain largely unknown. Combining observations from curli amyloidogenesis in bulk solutions with real-time in situ nanoscopic imaging at the single-fiber level, we show that curli display polar growth, and we detect two kinetic regimes of fiber elongation. Single fibers exhibit stop-and-go dynamics characterized by bursts of steady-state growth alternated with periods of stagnation...
June 19, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28628095/a-scaffold-protein-that-chaperones-a-cysteine-sulfenic-acid-in-h2o2-signaling
#3
Antoine Bersweiler, Benoît D'Autréaux, Hortense Mazon, Alexandre Kriznik, Gemma Belli, Agnès Delaunay-Moisan, Michel B Toledano, Sophie Rahuel-Clermont
In Saccharomyces cerevisiae, Yap1 regulates an H2O2-inducible transcriptional response that controls cellular H2O2 homeostasis. H2O2 activates Yap1 by oxidation through the intermediary of the thiol peroxidase Orp1. Upon reacting with H2O2, Orp1 catalytic cysteine oxidizes to a sulfenic acid, which then engages into either an intermolecular disulfide with Yap1, leading to Yap1 activation, or an intramolecular disulfide that commits the enzyme into its peroxidatic cycle. How the first of these two competing reactions, which is kinetically unfavorable, occurs was previously unknown...
June 19, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28628094/a-water-soluble-dsbb-variant-that-catalyzes-disulfide-bond-formation-in-vivo
#4
Dario Mizrachi, Michael-Paul Robinson, Guoping Ren, Na Ke, Mehmet Berkmen, Matthew P DeLisa
Escherichia coli DsbB is a transmembrane enzyme that catalyzes the reoxidation of the periplasmic oxidase DsbA by ubiquinone. Here, we sought to convert membrane-bound DsbB into a water-soluble biocatalyst by leveraging a previously described method for in vivo solubilization of integral membrane proteins (IMPs). When solubilized DsbB variants were coexpressed with an export-defective copy of DsbA in the cytoplasm of wild-type E. coli cells, artificial oxidation pathways were created that efficiently catalyzed de novo disulfide-bond formation in a range of substrate proteins, in a manner dependent on both DsbA and quinone...
June 19, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28628093/a-heme-dependent-enzyme-forms-the-nitrogen-nitrogen-bond-in-piperazate
#5
Yi-Ling Du, Hai-Yan He, Melanie A Higgins, Katherine S Ryan
Molecules containing a nitrogen-nitrogen (N-N) linkage have a variety of structures and biological activities; however, no enzyme has yet been demonstrated to catalyze N-N bond formation in an organic molecule. Here we report that the heme-dependent enzyme KtzT from Kutzneria sp. 744 catalyzes N-N bond formation in the biosynthesis of piperazate, a building block for nonribosomal peptides.
June 19, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28604697/site-specific-incorporation-of-phosphotyrosine-using-an-expanded-genetic-code
#6
Christian Hoppmann, Allison Wong, Bing Yang, Shuwei Li, Tony Hunter, Kevan M Shokat, Lei Wang
Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination...
June 12, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28604696/a-front-face-sni-synthase-engineered-from-a-retaining-double-sn2-hydrolase
#7
Javier Iglesias-Fernández, Susan M Hancock, Seung Seo Lee, Maola Khan, Jo Kirkpatrick, Neil J Oldham, Katherine McAuley, Anthony Fordham-Skelton, Carme Rovira, Benjamin G Davis
SNi-like mechanisms, which involve front-face leaving group departure and nucleophile approach, have been observed experimentally and computationally in chemical and enzymatic substitution at α-glycosyl electrophiles. Since SNi-like, SN1 and SN2 substitution pathways can be energetically comparable, engineered switching could be feasible. Here, engineering of Sulfolobus solfataricus β-glycosidase, which originally catalyzed double SN2 substitution, changed its mode to SNi-like. Destruction of the first SN2 nucleophile through E387Y mutation created a β-stereoselective catalyst for glycoside synthesis from activated substrates, despite lacking a nucleophile...
June 12, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28604695/a-scalable-platform-to-identify-fungal-secondary-metabolites-and-their-gene-clusters
#8
Kenneth D Clevenger, Jin Woo Bok, Rosa Ye, Galen P Miley, Maria H Verdan, Thomas Velk, Cynthia Chen, KaHoua Yang, Matthew T Robey, Peng Gao, Matthew Lamprecht, Paul M Thomas, Md Nurul Islam, Jonathan M Palmer, Chengcang C Wu, Nancy P Keller, Neil L Kelleher
The genomes of filamentous fungi contain up to 90 biosynthetic gene clusters (BGCs) encoding diverse secondary metabolites-an enormous reservoir of untapped chemical potential. However, the recalcitrant genetics, cryptic expression, and unculturability of these fungi prevent scientists from systematically exploiting these gene clusters and harvesting their products. As heterologous expression of fungal BGCs is largely limited to the expression of single or partial clusters, we established a scalable process for the expression of large numbers of full-length gene clusters, called FAC-MS...
June 12, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28604694/a-mutant-o-glcnacase-enriches-drosophila-developmental-regulators
#9
Nithya Selvan, Ritchie Williamson, Daniel Mariappa, David G Campbell, Robert Gourlay, Andrew T Ferenbach, Tonia Aristotelous, Iva Hopkins-Navratilova, Matthias Trost, Daan M F van Aalten
Protein O-GlcNAcylation is a reversible post-translational modification of serines and threonines on nucleocytoplasmic proteins. It is cycled by the enzymes O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (O-GlcNAcase or OGA). Genetic approaches in model organisms have revealed that protein O-GlcNAcylation is essential for early embryogenesis. The Drosophila melanogaster gene supersex combs (sxc), which encodes OGT, is a polycomb gene, whose null mutants display homeotic transformations and die at the pharate adult stage...
June 12, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28604693/genetically-encoding-phosphotyrosine-and-its-nonhydrolyzable-analog-in-bacteria
#10
Xiaozhou Luo, Guangsen Fu, Rongsheng E Wang, Xueyong Zhu, Claudio Zambaldo, Renhe Liu, Tao Liu, Xiaoxuan Lyu, Jintang Du, Weimin Xuan, Anzhi Yao, Sean A Reed, Mingchao Kang, Yuhan Zhang, Hui Guo, Chunhui Huang, Peng-Yu Yang, Ian A Wilson, Peter G Schultz, Feng Wang
Tyrosine phosphorylation is a common protein post-translational modification that plays a critical role in signal transduction and the regulation of many cellular processes. Using a propeptide strategy to increase cellular uptake of O-phosphotyrosine (pTyr) and its nonhydrolyzable analog 4-phosphomethyl-L-phenylalanine (Pmp), we identified an orthogonal aminoacyl-tRNA synthetase-tRNA pair that allows site-specific incorporation of both pTyr and Pmp into recombinant proteins in response to the amber stop codon in Escherichia coli in good yields...
June 12, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28604692/oxidation-of-phosphorothioate-dna-modifications-leads-to-lethal-genomic-instability
#11
Stefanie Kellner, Michael S DeMott, Ching Pin Cheng, Brandon S Russell, Bo Cao, Delin You, Peter C Dedon
Genomic modification by sulfur in the form of phosphorothioate (PT) is widespread among prokaryotes, including human pathogens. Apart from its physiological functions, PT sulfur has redox and nucleophilic properties that suggest effects on bacterial fitness in stressful environments. Here we show that PTs are dynamic and labile DNA modifications that cause genomic instability during oxidative stress. In experiments involving isotopic labeling coupled with mass spectrometry, we observed sulfur replacement in PTs at a rate of ∼2% h(-1) in unstressed Escherichia coli and Salmonella enterica...
June 12, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28581485/activity-based-probes-for-functional-interrogation-of-retaining-%C3%AE-glucuronidases
#12
Liang Wu, Jianbing Jiang, Yi Jin, Wouter W Kallemeijn, Chi-Lin Kuo, Marta Artola, Wei Dai, Cas van Elk, Marco van Eijk, Gijsbert A van der Marel, Jeroen D C Codée, Bogdan I Florea, Johannes M F G Aerts, Herman S Overkleeft, Gideon J Davies
Humans express at least two distinct β-glucuronidase enzymes that are involved in disease: exo-acting β-glucuronidase (GUSB), whose deficiency gives rise to mucopolysaccharidosis type VII, and endo-acting heparanase (HPSE), whose overexpression is implicated in inflammation and cancers. The medical importance of these enzymes necessitates reliable methods to assay their activities in tissues. Herein, we present a set of β-glucuronidase-specific activity-based probes (ABPs) that allow rapid and quantitative visualization of GUSB and HPSE in biological samples, providing a powerful tool for dissecting their activities in normal and disease states...
June 5, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28581484/autocatalytic-backbone-n-methylation-in-a-family-of-ribosomal-peptide-natural-products
#13
Niels S van der Velden, Noemi Kälin, Maximilian J Helf, Jörn Piel, Michael F Freeman, Markus Künzler
Peptide backbone N-methylation, as seen in cyclosporin A, has been considered to be exclusive to nonribosomal peptides. We have identified the first post-translationally modified peptide or protein harboring internal α-N-methylations through discovery of the genetic locus for the omphalotins, cyclic N-methylated peptides produced by the fungus Omphalotus olearius. We show that iterative autocatalytic activity of an N-methyltransferase fused to its peptide substrate is the signature of a new family of ribosomally encoded metabolites...
June 5, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28581483/blocking-an-n-terminal-acetylation-dependent-protein-interaction-inhibits-an-e3-ligase
#14
Daniel C Scott, Jared T Hammill, Jaeki Min, David Y Rhee, Michele Connelly, Vladislav O Sviderskiy, Deepak Bhasin, Yizhe Chen, Su-Sien Ong, Sergio C Chai, Asli N Goktug, Guochang Huang, Julie K Monda, Jonathan Low, Ho Shin Kim, Joao A Paulo, Joe R Cannon, Anang A Shelat, Taosheng Chen, Ian R Kelsall, Arno F Alpi, Vishwajeeth Pagala, Xusheng Wang, Junmin Peng, Bhuvanesh Singh, J Wade Harper, Brenda A Schulman, R Kip Guy
N-terminal acetylation is an abundant modification influencing protein functions. Because ∼80% of mammalian cytosolic proteins are N-terminally acetylated, this modification is potentially an untapped target for chemical control of their functions. Structural studies have revealed that, like lysine acetylation, N-terminal acetylation converts a positively charged amine into a hydrophobic handle that mediates protein interactions; hence, this modification may be a druggable target. We report the development of chemical probes targeting the N-terminal acetylation-dependent interaction between an E2 conjugating enzyme (UBE2M or UBC12) and DCN1 (DCUN1D1), a subunit of a multiprotein E3 ligase for the ubiquitin-like protein NEDD8...
June 5, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28581482/parallel-evolution-of-non-homologous-isofunctional-enzymes-in-methionine-biosynthesis
#15
Karine Bastard, Alain Perret, Aline Mariage, Thomas Bessonnet, Agnès Pinet-Turpault, Jean-Louis Petit, Ekaterina Darii, Pascal Bazire, Carine Vergne-Vaxelaire, Clémence Brewee, Adrien Debard, Virginie Pellouin, Marielle Besnard-Gonnet, François Artiguenave, Claudine Médigue, David Vallenet, Antoine Danchin, Anne Zaparucha, Jean Weissenbach, Marcel Salanoubat, Véronique de Berardinis
Experimental validation of enzyme function is crucial for genome interpretation, but it remains challenging because it cannot be scaled up to accommodate the constant accumulation of genome sequences. We tackled this issue for the MetA and MetX enzyme families, phylogenetically unrelated families of acyl-L-homoserine transferases involved in L-methionine biosynthesis. Members of these families are prone to incorrect annotation because MetA and MetX enzymes are assumed to always use acetyl-CoA and succinyl-CoA, respectively...
June 5, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28398287/crispr-cas9-strategy-for-activation-of-silent-streptomyces-biosynthetic-gene-clusters
#16
Mingzi M Zhang, Fong Tian Wong, Yajie Wang, Shangwen Luo, Yee Hwee Lim, Elena Heng, Wan Lin Yeo, Ryan E Cobb, Behnam Enghiad, Ee Lui Ang, Huimin Zhao
Here we report an efficient CRISPR-Cas9 knock-in strategy to activate silent biosynthetic gene clusters (BGCs) in streptomycetes. We applied this one-step strategy to activate multiple BGCs of different classes in five Streptomyces species and triggered the production of unique metabolites, including a novel pentangular type II polyketide in Streptomyces viridochromogenes. This potentially scalable strategy complements existing activation approaches and facilitates discovery efforts to uncover new compounds with interesting bioactivities...
April 10, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28632705/targeting-the-n-terminus-for-site-selective-protein-modification
#17
Christian B Rosen, Matthew B Francis
The formation of well-defined protein bioconjugates is critical for many studies and technologies in chemical biology. Tried-and-true methods for accomplishing this typically involve the targeting of cysteine residues, but the rapid growth of contemporary bioconjugate applications has required an expanded repertoire of modification techniques. One very powerful set of strategies involves the modification of proteins at their N termini, as these positions are typically solvent exposed and provide chemically distinct sites for many protein targets...
July 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28553949/functional-selectivity-of-gpcr-directed-drug-action-through-location-bias
#18
Roshanak Irannejad, Veronica Pessino, Delphine Mika, Bo Huang, Philip B Wedegaertner, Marco Conti, Mark von Zastrow
G-protein-coupled receptors (GPCRs) are increasingly recognized to operate from intracellular membranes as well as the plasma membrane. The β2-adrenergic GPCR can activate Gs-linked cyclic AMP (Gs-cAMP) signaling from endosomes. We show here that the homologous human β1-adrenergic receptor initiates an internal Gs-cAMP signal from the Golgi apparatus. By developing a chemical method to acutely squelch G-protein coupling at defined membrane locations, we demonstrate that Golgi activation contributes significantly to the overall cellular cAMP response...
July 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28553948/lipid-ii-overproduction-allows-direct-assay-of-transpeptidase-inhibition-by-%C3%AE-lactams
#19
Yuan Qiao, Veerasak Srisuknimit, Frederick Rubino, Kaitlin Schaefer, Natividad Ruiz, Suzanne Walker, Daniel Kahne
Peptidoglycan is an essential crosslinked polymer that surrounds bacteria and protects them from osmotic lysis. β-lactam antibiotics target the final stages of peptidoglycan biosynthesis by inhibiting the transpeptidases that crosslink glycan strands to complete cell wall assembly. Characterization of transpeptidases and their inhibition by β-lactams have been hampered by lack of access to a suitable substrate. We describe a general approach to accumulate Lipid II in bacteria and to obtain large quantities of this cell wall precursor...
July 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28553947/structural-basis-for-high-affinity-fluorophore-binding-and-activation-by-rna-mango
#20
Robert J Trachman, Natalia A Demeshkina, Matthew W L Lau, Shanker Shyam S Panchapakesan, Sunny C Y Jeng, Peter J Unrau, Adrian R Ferré-D'Amaré
Genetically encoded fluorescent protein tags have revolutionized proteome studies, whereas the lack of intrinsically fluorescent RNAs has hindered transcriptome exploration. Among several RNA-fluorophore complexes that potentially address this problem, RNA Mango has an exceptionally high affinity for its thiazole orange (TO)-derived fluorophore, TO1-Biotin (Kd ∼3 nM), and, in complex with related ligands, it is one of the most redshifted fluorescent macromolecular tags known. To elucidate how this small aptamer exhibits such properties, which make it well suited for studying low-copy cellular RNAs, we determined its 1...
July 2017: Nature Chemical Biology
journal
journal
40837
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"