Ubiquinone accumulation improves osmotic-stress tolerance in Escherichia coli.

abstract：:Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an ...

journal_title：Nature chemical biology

authors： Bradshaw JM,McFarland JM,Paavilainen VO,Bisconte A,Tam D,Phan VT,Romanov S,Finkle D,Shu J,Patel V,Ton T,Li X,Loughhead DG,Nunn PA,Karr DE,Gerritsen ME,Funk JO,Owens TD,Verner E,Brameld KA,Hill RJ,Goldstein DM,

更新日期：2015-07-01 00:00:00

abstract：:Proper gene expression is essential for the survival of every cell. Once thought to be a passive transporter of genetic information, RNA has recently emerged as a key player in nearly every pathway in the cell. A full description of its structure is critical to understanding RNA function. Decades of research have focu...

journal_title：Nature chemical biology

authors： Kubota M,Tran C,Spitale RC

更新日期：2015-12-01 00:00:00

abstract：:Directly modulating the activity of genome-editing proteins has the potential to increase their specificity by reducing activity following target locus modification. We developed Cas9 nucleases that are activated by the presence of a cell-permeable small molecule by inserting an evolved 4-hydroxytamoxifen-responsive i...

journal_title：Nature chemical biology

authors： Davis KM,Pattanayak V,Thompson DB,Zuris JA,Liu DR

更新日期：2015-05-01 00:00:00

abstract：:F(1)-ATPase is an ATP-driven rotary motor protein in which the γ-subunit rotates against the catalytic stator ring. Although the reaction scheme of F(1) has mostly been revealed, the timing of inorganic phosphate (P(i)) release remains controversial. Here we addressed this issue by verifying the reversibility of ATP h...

journal_title：Nature chemical biology

authors： Watanabe R,Iino R,Noji H

更新日期：2010-11-01 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：:SB269652 is to our knowledge the first drug-like allosteric modulator of the dopamine D2 receptor (D2R), but it contains structural features associated with orthosteric D2R antagonists. Using a functional complementation system to control the identity of individual protomers within a dimeric D2R complex, we converted ...

journal_title：Nature chemical biology

authors： Lane JR,Donthamsetti P,Shonberg J,Draper-Joyce CJ,Dentry S,Michino M,Shi L,López L,Scammells PJ,Capuano B,Sexton PM,Javitch JA,Christopoulos A

更新日期：2014-09-01 00:00:00

abstract：:Jasmonates are lipid-derived plant hormones that regulate plant defenses and numerous developmental processes. Although the biosynthesis and molecular function of the most active form of the hormone, (+)-7-iso-jasmonoyl-L-isoleucine (JA-Ile), have been unraveled, it remains poorly understood how the diversity of bioac...

journal_title：Nature chemical biology

authors： Meesters C,Mönig T,Oeljeklaus J,Krahn D,Westfall CS,Hause B,Jez JM,Kaiser M,Kombrink E

更新日期：2014-10-01 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：:Regulation of gene expression in response to the changing environment is critical for cell survival. For instance, binding of macrolide antibiotics to the ribosome promotes translation arrest at the leader open reading frames ermCL and ermBL, which is necessary for inducing the antibiotic resistance genes ermC and erm...

journal_title：Nature chemical biology

authors： Gupta P,Liu B,Klepacki D,Gupta V,Schulten K,Mankin AS,Vázquez-Laslop N

更新日期：2016-03-01 00:00:00

abstract：:Inorganic nitrite (NO(2)(-)) is emerging as a regulator of physiological functions and tissue responses to ischemia, whereas the more stable nitrate anion (NO(3)(-)) is generally considered to be biologically inert. Bacteria express nitrate reductases that produce nitrite, but mammals lack these specific enzymes. Here...

journal_title：Nature chemical biology

authors： Jansson EA,Huang L,Malkey R,Govoni M,Nihlén C,Olsson A,Stensdotter M,Petersson J,Holm L,Weitzberg E,Lundberg JO

更新日期：2008-07-01 00:00:00

abstract：:The lasso peptide microcin J25 is known to hijack the siderophore receptor FhuA for initiating internalization. Here, we provide what is to our knowledge the first structural evidence on the recognition mechanism, and our biochemical data show that another closely related lasso peptide cannot interact with FhuA. Our w...

journal_title：Nature chemical biology

authors： Mathavan I,Zirah S,Mehmood S,Choudhury HG,Goulard C,Li Y,Robinson CV,Rebuffat S,Beis K

更新日期：2014-05-01 00:00:00

abstract：:The plant hormone auxin regulates virtually every aspect of plant growth and development. Auxin acts by binding the F-box protein transport inhibitor response 1 (TIR1) and promotes the degradation of the AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) transcriptional repressors. Here we show that efficient auxin binding requires...

journal_title：Nature chemical biology

authors： Calderón Villalobos LI,Lee S,De Oliveira C,Ivetac A,Brandt W,Armitage L,Sheard LB,Tan X,Parry G,Mao H,Zheng N,Napier R,Kepinski S,Estelle M

更新日期：2012-04-01 00:00:00

abstract：:The eukaryotic 26S proteasome controls cellular processes by degrading specific regulatory proteins. Most proteins are targeted for degradation by a signal or degron that consists of two parts: a proteasome-binding tag, typically covalently attached polyubiquitin chains, and an unstructured region that serves as the i...

journal_title：Nature chemical biology

authors： Inobe T,Fishbain S,Prakash S,Matouschek A

更新日期：2011-03-01 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：:Binding to the primary receptor, CD4, triggers conformational changes in the metastable HIV-1 envelope glycoprotein (Env) trimer ((gp120-gp41)3) that are important for virus entry into host cells. These changes include an 'opening' of the trimer, creation of a binding site for the CCR5 co-receptor and formation and/or...

journal_title：Nature chemical biology

authors： Herschhorn A,Gu C,Espy N,Richard J,Finzi A,Sodroski JG

更新日期：2014-10-01 00:00:00

abstract：:Transcription factors have diverse roles during embryonic development, combinatorially controlling cellular states in a spatially and temporally defined manner. Resolving the dynamic transcriptional profiles that underlie these patterning processes is essential for understanding embryogenesis at the molecular level. H...

journal_title：Nature chemical biology

authors： Shestopalov IA,Pitt CL,Chen JK

更新日期：2012-01-29 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：:Small molecules that specifically activate an intracellular protein of interest are highly desirable. A generally applicable strategy, however, remains elusive. Herein we describe a small molecule-triggered bioorthogonal protein decaging technique that relies on the inverse electron-demand Diels-Alder reaction for eli...

journal_title：Nature chemical biology

authors： Li J,Jia S,Chen PR

更新日期：2014-12-01 00:00:00

abstract：:Accumulation of unfolded proteins within the endoplasmic reticulum (ER) of eukaryotic cells leads to an unfolded protein response (UPR) that either restores homeostasis or commits the cells to apoptosis. Tools traditionally used to study the UPR are proapoptotic and thus confound analysis of long-term cellular respons...

journal_title：Nature chemical biology

authors： Raina K,Noblin DJ,Serebrenik YV,Adams A,Zhao C,Crews CM

更新日期：2014-11-01 00:00:00

abstract：:Liver X receptors (Lxrα and Lxrβ) are ligand-dependent nuclear receptors critical for ventral midbrain neurogenesis in vivo. However, no endogenous midbrain Lxr ligand has so far been identified. Here we used LC/MS and functional assays to identify cholic acid as a new Lxr ligand. Moreover, 24(S),25-epoxycholesterol (...

journal_title：Nature chemical biology

authors： Theofilopoulos S,Wang Y,Kitambi SS,Sacchetti P,Sousa KM,Bodin K,Kirk J,Saltó C,Gustafsson M,Toledo EM,Karu K,Gustafsson JÅ,Steffensen KR,Ernfors P,Sjövall J,Griffiths WJ,Arenas E

更新日期：2013-02-01 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：:Many protein kinases are key nodal signaling molecules that regulate a wide range of cellular functions. These functions may require complex spatiotemporal regulation of kinase activities. Here, we show that protein kinase A (PKA), Ca(2+) and cyclic AMP (cAMP) oscillate in sync in insulin-secreting MIN6 beta cells, fo...

journal_title：Nature chemical biology

authors： Ni Q,Ganesan A,Aye-Han NN,Gao X,Allen MD,Levchenko A,Zhang J

更新日期：2011-01-01 00:00:00

abstract：:This Commentary clarifies the meaning of the funnel diagram, which has been widely cited in papers on protein folding. To aid in the analysis of the funnel diagram, this Commentary reviews historical approaches to understanding the mechanism of protein folding. The primary role of free energy in protein folding is dis...

journal_title：Nature chemical biology

authors： Karplus M

更新日期：2011-06-17 00:00:00

abstract：:To maximize a desired product, metabolic engineers typically express enzymes to high, constant levels. Yet, permanent pathway activation can have undesirable consequences including competition with essential pathways and accumulation of toxic intermediates. Faced with similar challenges, natural metabolic systems comp...

journal_title：Nature chemical biology

authors： Zhao EM,Suek N,Wilson MZ,Dine E,Pannucci NL,Gitai Z,Avalos JL,Toettcher JE

更新日期：2019-06-01 00:00:00

abstract：:Intracellular Ca(2+) regulates numerous proteins and cellular functions and can vary substantially over submicron and submillisecond scales, so precisely localized fast detection is desirable. We have created a approximately 1-kDa biarsenical Ca(2+) indicator, called Calcium Green FlAsH (CaGF, 1), to probe [Ca(2+)] su...

journal_title：Nature chemical biology

authors： Tour O,Adams SR,Kerr RA,Meijer RM,Sejnowski TJ,Tsien RW,Tsien RY

更新日期：2007-07-01 00:00:00

abstract：:Mucopolysaccharidosis type I (MPS I), caused by mutations in the gene encoding α-L-iduronidase (IDUA), is one of approximately 70 genetic disorders collectively known as the lysosomal storage diseases. To gain insight into the basis for MPS I, we crystallized human IDUA produced in an Arabidopsis thaliana cgl mutant. ...

journal_title：Nature chemical biology

authors： Bie H,Yin J,He X,Kermode AR,Goddard-Borger ED,Withers SG,James MN

更新日期：2013-11-01 00:00:00

abstract：:Pseudouridine synthases (PUSs) are responsible for installation of pseudouridine (Ψ) modification in RNA. However, the activity and function of the PUS enzymes remain largely unexplored. Here we focus on human PUS10 and find that it co-expresses with the microprocessor (DROSHA-DGCR8 complex). Depletion of PUS10 result...

journal_title：Nature chemical biology

authors： Song J,Zhuang Y,Zhu C,Meng H,Lu B,Xie B,Peng J,Li M,Yi C

更新日期：2020-02-01 00:00:00

abstract：:MicroRNAs are evolutionarily conserved small, noncoding RNAs that regulate diverse biological processes. Due to their essential regulatory roles, microRNA biogenesis is tightly regulated, where protein factors are often found to interact with specific primary and precursor microRNAs for regulation. Here, using NMR rel...

journal_title：Nature chemical biology

authors： Baisden JT,Boyer JA,Zhao B,Hammond SM,Zhang Q

更新日期：2021-01-01 00:00:00

abstract：:Synthetic mRNA is an attractive vehicle for gene therapies because of its transient nature and improved safety profile over DNA. However, unlike DNA, broadly applicable methods to control expression from mRNA are lacking. Here we describe a platform for small-molecule-based regulation of expression from modified RNA (...

journal_title：Nature chemical biology

authors： Wagner TE,Becraft JR,Bodner K,Teague B,Zhang X,Woo A,Porter E,Alburquerque B,Dobosh B,Andries O,Sanders NN,Beal J,Densmore D,Kitada T,Weiss R

更新日期：2018-11-01 00:00:00

abstract：:The N-end rule pathway senses the N-terminal destabilizing residues of degradation substrates for the ubiquitin-proteasome system, whose integrity shields against various human syndromes including cancer and cardiovascular diseases. GID4, a subunit of the ubiquitin ligase GID complex, has been recently identified as t...

journal_title：Nature chemical biology

authors： Dong C,Zhang H,Li L,Tempel W,Loppnau P,Min J

更新日期：2018-05-01 00:00:00