abstract：:The discovery of functional RNAs that are critical for normal and disease physiology continues to expand at a breakneck pace. Many RNA functions are controlled by the formation of specific structures, and an understanding of each structural component is necessary to elucidate its function. Measuring solvent accessibil...

journal_title：Nature chemical biology

authors： Feng C,Chan D,Joseph J,Muuronen M,Coldren WH,Dai N,Corrêa IR Jr,Furche F,Hadad CM,Spitale RC

更新日期：2018-03-01 00:00:00

abstract：:The phytohormone auxin indole-3-acetic acid (IAA) regulates nearly all aspects of plant growth and development. Despite substantial progress in our understanding of auxin biology, delineating specific auxin response remains a major challenge. Auxin regulates transcriptional response via its receptors, TIR1 and AFB F-b...

journal_title：Nature chemical biology

authors： Uchida N,Takahashi K,Iwasaki R,Yamada R,Yoshimura M,Endo TA,Kimura S,Zhang H,Nomoto M,Tada Y,Kinoshita T,Itami K,Hagihara S,Torii KU

更新日期：2018-03-01 00:00:00

abstract：:Methylation of nucleotides in ribosomal RNAs (rRNAs) is a ubiquitous feature that occurs in all living organisms. Identification of all enzymes responsible for rRNA methylation, as well as mapping of all modified rRNA residues, is now complete for a number of model species, such as Escherichia coli and Saccharomyces c...

journal_title：Nature chemical biology

authors： Sergiev PV,Aleksashin NA,Chugunova AA,Polikanov YS,Dontsova OA

更新日期：2018-02-14 00:00:00

abstract：:Cyclin-dependent kinase 9 (CDK9), an important regulator of transcriptional elongation, is a promising target for cancer therapy, particularly for cancers driven by transcriptional dysregulation. We characterized NVP-2, a selective ATP-competitive CDK9 inhibitor, and THAL-SNS-032, a selective CDK9 degrader consisting ...

journal_title：Nature chemical biology

authors： Olson CM,Jiang B,Erb MA,Liang Y,Doctor ZM,Zhang Z,Zhang T,Kwiatkowski N,Boukhali M,Green JL,Haas W,Nomanbhoy T,Fischer ES,Young RA,Bradner JE,Winter GE,Gray NS

更新日期：2018-02-01 00:00:00

abstract：:Chemistry drives many biological interactions between the microbiota and host animals, yet it is often challenging to identify the chemicals involved. This poses a problem, as such small molecules are excellent sources of potential pharmaceuticals, pretested by nature for animal compatibility. We discovered anti-HIV c...

journal_title：Nature chemical biology

authors： Smith TE,Pond CD,Pierce E,Harmer ZP,Kwan J,Zachariah MM,Harper MK,Wyche TP,Matainaho TK,Bugni TS,Barrows LR,Ireland CM,Schmidt EW

更新日期：2018-02-01 00:00:00

abstract：:Enzyme-catalyzed peptide ligation is a powerful tool for site-specific protein bioconjugation, but stringent enzyme-substrate specificity limits its utility. We developed an approach for comprehensively characterizing peptide ligase specificity for N termini using proteome-derived peptide libraries. We used this strat...

journal_title：Nature chemical biology

authors： Weeks AM,Wells JA

更新日期：2018-01-01 00:00:00

abstract：:Targeted drugs are effective when they directly inhibit strong disease drivers, but only a small fraction of diseases feature defined actionable drivers. Alternatively, network-based approaches can uncover new therapeutic opportunities. Applying an integrated phenotypic screening, chemical and phosphoproteomics strate...

journal_title：Nature chemical biology

authors： Kuenzi BM,Remsing Rix LL,Stewart PA,Fang B,Kinose F,Bryant AT,Boyle TA,Koomen JM,Haura EB,Rix U

更新日期：2017-12-01 00:00:00

abstract：:Small ubiquitin-like modifier (SUMO) family proteins regulate target-protein functions by post-translational modification. However, a potent and selective inhibitor targeting the SUMO pathway has been lacking. Here we describe ML-792, a mechanism-based SUMO-activating enzyme (SAE) inhibitor with nanomolar potency in c...

journal_title：Nature chemical biology

authors： He X,Riceberg J,Soucy T,Koenig E,Minissale J,Gallery M,Bernard H,Yang X,Liao H,Rabino C,Shah P,Xega K,Yan ZH,Sintchak M,Bradley J,Xu H,Duffey M,England D,Mizutani H,Hu Z,Guo J,Chau R,Dick LR,Brownell JE,Ne

更新日期：2017-11-01 00:00:00

abstract：:The GATOR1 (SEACIT) complex consisting of Iml1-Npr2-Npr3 inhibits target of rapamycin complex 1 (TORC1) in response to amino acid insufficiency. In glucose medium, Saccharomyces cerevisiae mutants lacking the function of this complex grow poorly in the absence of amino acid supplementation, despite showing hallmarks o...

journal_title：Nature chemical biology

authors： Chen J,Sutter BM,Shi L,Tu BP

更新日期：2017-11-01 00:00:00

abstract：:Twister is a small ribozyme present in almost all kingdoms of life that rapidly self-cleaves in variety of divalent metal ions. We used activity assays, bulk FRET and single-molecule FRET (smFRET) to understand how different metal ions promote folding and self-cleavage of the Oryza sativa twister ribozyme. Although mo...

journal_title：Nature chemical biology

authors： Panja S,Hua B,Zegarra D,Ha T,Woodson SA

更新日期：2017-10-01 00:00:00

abstract：:DNA polymerases catalyze efficient and high-fidelity DNA synthesis. While this reaction favors nucleotide incorporation, polymerases also catalyze a reverse reaction, pyrophosphorolysis, that removes the DNA primer terminus and generates deoxynucleoside triphosphates. Because pyrophosphorolysis can influence polymeras...

journal_title：Nature chemical biology

authors： Shock DD,Freudenthal BD,Beard WA,Wilson SH

更新日期：2017-10-01 00:00:00

abstract：:Kinetochores act as hubs for multiple activities during cell division, including microtubule interactions and spindle checkpoint signaling. Each kinetochore can act autonomously, and activities change rapidly as proteins are recruited to, or removed from, kinetochores. Understanding this dynamic system requires tools ...

journal_title：Nature chemical biology

authors： Zhang H,Aonbangkhen C,Tarasovetc EV,Ballister ER,Chenoweth DM,Lampson MA

更新日期：2017-10-01 00:00:00

abstract：:Thioredoxin (Trx) is one of the two major thiol antioxidants, playing essential roles in redox homeostasis and signaling. Despite its importance, there is a lack of methods for monitoring Trx redox dynamics in live cells, hindering a better understanding of physiological and pathological roles of the Trx redox system....

journal_title：Nature chemical biology

authors： Fan Y,Makar M,Wang MX,Ai HW

更新日期：2017-09-01 00:00:00

abstract：:Thiolutin is a disulfide-containing antibiotic and anti-angiogenic compound produced by Streptomyces. Its biological targets are not known. We show that reduced thiolutin is a zinc chelator that inhibits the JAB1/MPN/Mov34 (JAMM) domain-containing metalloprotease Rpn11, a deubiquitinating enzyme of the 19S proteasome....

journal_title：Nature chemical biology

authors： Lauinger L,Li J,Shostak A,Cemel IA,Ha N,Zhang Y,Merkl PE,Obermeyer S,Stankovic-Valentin N,Schafmeier T,Wever WJ,Bowers AA,Carter KP,Palmer AE,Tschochner H,Melchior F,Deshaies RJ,Brunner M,Diernfellner A

更新日期：2017-07-01 00:00:00

abstract：:Miniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPα-Tyr, a designed peptide comprising an α-helix buttressed by a polyproline II helix. PPα-Tyr is water soluble and monomeric, and it unfolds cooperatively with a midpoint unfolding...

journal_title：Nature chemical biology

authors： Baker EG,Williams C,Hudson KL,Bartlett GJ,Heal JW,Porter Goff KL,Sessions RB,Crump MP,Woolfson DN

更新日期：2017-07-01 00:00:00

abstract：:The nematode Caenorhabditis elegans requires exogenous cholesterol to survive and its depletion leads to early developmental arrest. Thus, tight regulation of cholesterol storage and distribution within the organism is indispensable. Here, we present a novel class of C. elegans phosphorylated glycosphingolipids, phosp...

journal_title：Nature chemical biology

authors： Boland S,Schmidt U,Zagoriy V,Sampaio JL,Fritsche RF,Czerwonka R,Lübken T,Reimann J,Penkov S,Knölker HJ,Kurzchalia TV

更新日期：2017-06-01 00:00:00

abstract：:Biotin is an essential vitamin in plants and mammals, functioning as the carbon dioxide carrier within central lipid metabolism. Bacterial pimeloyl-CoA synthetase (BioW) acts as a highly specific substrate-selection gate, ensuring the integrity of the carbon chain in biotin synthesis. BioW catalyzes the condensation o...

journal_title：Nature chemical biology

authors： Wang M,Moynié L,Harrison PJ,Kelly V,Piper A,Naismith JH,Campopiano DJ

更新日期：2017-06-01 00:00:00

abstract：:Naturally produced polybrominated diphenyl ethers (PBDEs) pervade the marine environment and structurally resemble toxic man-made brominated flame retardants. PBDEs bioaccumulate in marine animals and are likely transferred to the human food chain. However, the biogenic basis for PBDE production in one of their most p...

journal_title：Nature chemical biology

authors： Agarwal V,Blanton JM,Podell S,Taton A,Schorn MA,Busch J,Lin Z,Schmidt EW,Jensen PR,Paul VJ,Biggs JS,Golden JW,Allen EE,Moore BS

更新日期：2017-05-01 00:00:00

abstract：:The catalytic activity of many protein kinases is controlled by conformational changes of a conserved Asp-Phe-Gly (DFG) motif. We used an infrared probe to track the DFG motif of the mitotic kinase Aurora A (AurA) and found that allosteric activation by the spindle-associated protein Tpx2 involves an equilibrium shift...

journal_title：Nature chemical biology

authors： Cyphers S,Ruff EF,Behr JM,Chodera JD,Levinson NM

更新日期：2017-04-01 00:00:00

abstract：:In this study, we demonstrate the feasibility of expanding the genetic code of Escherichia coli using its own tryptophanyl-tRNA synthetase and tRNA (TrpRS-tRNATrp) pair. This was made possible by first functionally replacing this endogenous pair with an E. coli-optimized counterpart from Saccharomyces cerevisiae, and ...

journal_title：Nature chemical biology

authors： Italia JS,Addy PS,Wrobel CJ,Crawford LA,Lajoie MJ,Zheng Y,Chatterjee A

更新日期：2017-04-01 00:00:00

abstract：:ADP-ribosylation is a post-translational modification that is known to be involved in cellular homeostasis and stress but has been challenging to analyze biochemically. To facilitate the detection of ADP-ribosylated proteins, we show that an alkyne-adenosine analog, N6-propargyl adenosine (N6pA), is metabolically inco...

journal_title：Nature chemical biology

authors： Westcott NP,Fernandez JP,Molina H,Hang HC

更新日期：2017-03-01 00:00:00

abstract：:Controlled distribution of lipids across various cell membranes is crucial for cell homeostasis and regulation. We developed an imaging method that allows simultaneous in situ quantification of cholesterol in two leaflets of the plasma membrane (PM) using tunable orthogonal cholesterol sensors. Our imaging revealed ma...

journal_title：Nature chemical biology

authors： Liu SL,Sheng R,Jung JH,Wang L,Stec E,O'Connor MJ,Song S,Bikkavilli RK,Winn RA,Lee D,Baek K,Ueda K,Levitan I,Kim KP,Cho W

更新日期：2017-03-01 00:00:00

abstract：:Long noncoding RNAs (lncRNAs) are important for gene expression, but little is known about their structures. RepA is a 1.6-kb mouse lncRNA comprising the same sequence as the 5' region of Xist, including A and F repeats. It has been proposed to facilitate the initiation and spread of X-chromosome inactivation, althoug...

journal_title：Nature chemical biology

authors： Liu F,Somarowthu S,Pyle AM

更新日期：2017-03-01 00:00:00

abstract：:N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (...

journal_title：Nature chemical biology

authors： Liu TW,Myschyshyn M,Sinclair DA,Cecioni S,Beja K,Honda BM,Morin RD,Vocadlo DJ

更新日期：2017-02-01 00:00:00

abstract：:Hundreds of human proteins are modified by reversible palmitoylation of cysteine residues (S-palmitoylation), but the regulation of depalmitoylation is poorly understood. Here, we develop 'depalmitoylation probes' (DPPs), small-molecule fluorophores, to monitor the endogenous activity levels of 'erasers' of S-palmitoy...

journal_title：Nature chemical biology

authors： Kathayat RS,Elvira PD,Dickinson BC

更新日期：2017-02-01 00:00:00

abstract：:Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, ...

journal_title：Nature chemical biology

authors： Rzuczek SG,Colgan LA,Nakai Y,Cameron MD,Furling D,Yasuda R,Disney MD

更新日期：2017-02-01 00:00:00

abstract：:RNA G-quadruplex (G4) structures are thought to affect biological processes, including translation and pre-mRNA splicing, but it is not possible at present to demonstrate that they form naturally at specific sequences in long functional RNA molecules. We developed a new strategy, footprinting of long 7-deazaguanine-su...

journal_title：Nature chemical biology

authors： Weldon C,Behm-Ansmant I,Hurley LH,Burley GA,Branlant C,Eperon IC,Dominguez C

更新日期：2017-01-01 00:00:00

abstract：:Ferroptosis is a form of regulated necrotic cell death controlled by glutathione peroxidase 4 (GPX4). At present, mechanisms that could predict sensitivity and/or resistance and that may be exploited to modulate ferroptosis are needed. We applied two independent approaches-a genome-wide CRISPR-based genetic screen and...

journal_title：Nature chemical biology

authors： Doll S,Proneth B,Tyurina YY,Panzilius E,Kobayashi S,Ingold I,Irmler M,Beckers J,Aichler M,Walch A,Prokisch H,Trümbach D,Mao G,Qu F,Bayir H,Füllekrug J,Scheel CH,Wurst W,Schick JA,Kagan VE,Angeli JP,Conrad M

更新日期：2017-01-01 00:00:00

abstract：:ADP-ribosylation (ADPr) is a biologically and clinically important post-translational modification, but little is known about the amino acids it targets on cellular proteins. Here we present a proteomic approach for direct in vivo identification and quantification of ADPr sites on histones. We have identified 12 uniqu...

journal_title：Nature chemical biology

authors： Leidecker O,Bonfiglio JJ,Colby T,Zhang Q,Atanassov I,Zaja R,Palazzo L,Stockum A,Ahel I,Matic I

更新日期：2016-12-01 00:00:00

abstract：:Here we present a natural product discovery approach, whereby structures are bioinformatically predicted from primary sequence and produced by chemical synthesis (synthetic-bioinformatic natural products, syn-BNPs), circumventing the need for bacterial culture and gene expression. When we applied the approach to nonri...

journal_title：Nature chemical biology

authors： Chu J,Vila-Farres X,Inoyama D,Ternei M,Cohen LJ,Gordon EA,Reddy BV,Charlop-Powers Z,Zebroski HA,Gallardo-Macias R,Jaskowski M,Satish S,Park S,Perlin DS,Freundlich JS,Brady SF

更新日期：2016-12-01 00:00:00

abstract：:Only 25% of bacterial membrane transporters have functional annotation owing to the difficulty of experimental study and of accurate prediction of their function. Here we report a sequence-independent method for high-throughput mining of novel transporters. The method is based on ligand-responsive biosensor systems th...

journal_title：Nature chemical biology

authors： Genee HJ,Bali AP,Petersen SD,Siedler S,Bonde MT,Gronenberg LS,Kristensen M,Harrison SJ,Sommer MO

更新日期：2016-12-01 00:00:00

abstract：:The With-No-Lysine (K) (WNK) kinases play a critical role in blood pressure regulation and body fluid and electrolyte homeostasis. Herein, we introduce the first orally bioavailable pan-WNK-kinase inhibitor, WNK463, that exploits unique structural features of the WNK kinases for both affinity and kinase selectivity. I...

journal_title：Nature chemical biology

authors： Yamada K,Park HM,Rigel DF,DiPetrillo K,Whalen EJ,Anisowicz A,Beil M,Berstler J,Brocklehurst CE,Burdick DA,Caplan SL,Capparelli MP,Chen G,Chen W,Dale B,Deng L,Fu F,Hamamatsu N,Harasaki K,Herr T,Hoffmann P,Hu QY,

更新日期：2016-11-01 00:00:00

abstract：:CRISPR-Cas9 has emerged as a powerful technology that enables ready modification of the mammalian genome. The ability to modulate Cas9 activity can reduce off-target cleavage and facilitate precise genome engineering. Here we report the development of a Cas9 variant whose activity can be switched on and off in human c...

journal_title：Nature chemical biology

authors： Liu KI,Ramli MN,Woo CW,Wang Y,Zhao T,Zhang X,Yim GR,Chong BY,Gowher A,Chua MZ,Jung J,Lee JH,Tan MH

更新日期：2016-11-01 00:00:00

abstract：:The structure-specific nuclease human flap endonuclease-1 (hFEN1) plays a key role in DNA replication and repair and may be of interest as an oncology target. We present the crystal structure of inhibitor-bound hFEN1, which shows a cyclic N-hydroxyurea bound in the active site coordinated to two magnesium ions. Three ...

journal_title：Nature chemical biology

authors： Exell JC,Thompson MJ,Finger LD,Shaw SJ,Debreczeni J,Ward TA,McWhirter C,Siöberg CL,Martinez Molina D,Abbott WM,Jones CD,Nissink JW,Durant ST,Grasby JA

更新日期：2016-10-01 00:00:00

abstract：:Oxidation of methionine disrupts the structure and function of a range of proteins, but little is understood about the chemistry that underlies these perturbations. Using quantum mechanical calculations, we found that oxidation increased the strength of the methionine-aromatic interaction motif, a driving force for pr...

journal_title：Nature chemical biology

authors： Lewis AK,Dunleavy KM,Senkow TL,Her C,Horn BT,Jersett MA,Mahling R,McCarthy MR,Perell GT,Valley CC,Karim CB,Gao J,Pomerantz WC,Thomas DD,Cembran A,Hinderliter A,Sachs JN

更新日期：2016-10-01 00:00:00

abstract：:RNA capping and decapping are thought to be distinctive features of eukaryotes. The redox cofactor NAD was recently discovered to be attached to small regulatory RNAs in bacteria in a cap-like manner, and Nudix hydrolase NudC was found to act as a NAD-decapping enzyme in vitro and in vivo. Here, crystal structures of ...

journal_title：Nature chemical biology

authors： Höfer K,Li S,Abele F,Frindert J,Schlotthauer J,Grawenhoff J,Du J,Patel DJ,Jäschke A

更新日期：2016-09-01 00:00:00

abstract：:Improved methods for studying intracellular reactive Fe(II) are of significant interest for studies of iron metabolism and disease-relevant changes in iron homeostasis. Here we describe a highly selective reactivity-based probe in which a Fenton-type reaction with intracellular labile Fe(II) leads to unmasking of the ...

journal_title：Nature chemical biology

authors： Spangler B,Morgan CW,Fontaine SD,Vander Wal MN,Chang CJ,Wells JA,Renslo AR

更新日期：2016-09-01 00:00:00

abstract：:More than 30 years ago, a calcium-dependent enzyme activity was described that generates N-acyl phosphatidylethanolamines (NAPEs), which are precursors for N-acyl ethanolamine (NAE) lipid transmitters, including the endocannabinoid anandamide. The identity of this calcium-dependent N-acyltransferase (Ca-NAT) has remai...

journal_title：Nature chemical biology

authors： Ogura Y,Parsons WH,Kamat SS,Cravatt BF

更新日期：2016-09-01 00:00:00

abstract：:A 2.4-Å-resolution X-ray crystal structure of the carrier-protein-independent halogenase WelO5 in complex with its welwitindolinone precursor substrate, 12-epi-fischerindole U, reveals that the C13 chlorination target is proximal to the anticipated site of the oxo group in a presumptive cis-halo-oxo-iron(IV) (haloferr...

journal_title：Nature chemical biology

authors： Mitchell AJ,Zhu Q,Maggiolo AO,Ananth NR,Hillwig ML,Liu X,Boal AK

更新日期：2016-08-01 00:00:00

abstract：:Conditional cooperativity is a common mechanism involved in transcriptional regulation of prokaryotic type II toxin-antitoxin operons and is intricately related to bacterial persistence. It allows the toxin component of a toxin-antitoxin module to act as a co-repressor at low doses of toxin as compared to antitoxin. W...

journal_title：Nature chemical biology

authors： Garcia-Pino A,De Gieter S,Talavera A,De Greve H,Efremov RG,Loris R

更新日期：2016-07-01 00:00:00