abstract：:Protein kinase signaling along the kinetochore-centromere axis is crucial to assure mitotic fidelity, yet the details of its spatial coordination are obscure. Here, we examined how pools of human Polo-like kinase 1 (Plk1) within this axis control signaling events to elicit mitotic functions. To do this, we restricted ...

journal_title：Nature chemical biology

authors： Lera RF,Potts GK,Suzuki A,Johnson JM,Salmon ED,Coon JJ,Burkard ME

更新日期：2016-06-01 00:00:00

abstract：:We engineered a photoactivatable system for rapidly and reversibly exporting proteins from the nucleus by embedding a nuclear export signal in the LOV2 domain from phototropin 1. Fusing the chromatin modifier Bre1 to the photoswitch, we achieved light-dependent control of histone H2B monoubiquitylation in yeast, revea...

journal_title：Nature chemical biology

authors： Yumerefendi H,Lerner AM,Zimmerman SP,Hahn K,Bear JE,Strahl BD,Kuhlman B

更新日期：2016-06-01 00:00:00

abstract：:Serine is both a proteinogenic amino acid and the source of one-carbon units essential for de novo purine and deoxythymidine synthesis. In the canonical pathway of glucose-derived serine synthesis, Homo sapiens phosphoglycerate dehydrogenase (PHGDH) catalyzes the first, rate-limiting step. Genetic loss of PHGDH is tox...

journal_title：Nature chemical biology

authors： Pacold ME,Brimacombe KR,Chan SH,Rohde JM,Lewis CA,Swier LJ,Possemato R,Chen WW,Sullivan LB,Fiske BP,Cho S,Freinkman E,Birsoy K,Abu-Remaileh M,Shaul YD,Liu CM,Zhou M,Koh MJ,Chung H,Davidson SM,Luengo A,Wang AQ,

更新日期：2016-06-01 00:00:00

abstract：:Biosynthesis enables renewable production of manifold compounds, yet often biosynthetic performance must be improved for it to be economically feasible. Nongenetic, cell-to-cell variations in protein and metabolite concentrations are naturally inherent, suggesting the existence of both high- and low-performance varian...

journal_title：Nature chemical biology

authors： Xiao Y,Bowen CH,Liu D,Zhang F

更新日期：2016-05-01 00:00:00

abstract：:N(1)-Methyladenosine (m(1)A) is a prevalent post-transcriptional RNA modification, yet little is known about its abundance, topology and dynamics in mRNA. Here, we show that m(1)A is prevalent in Homo sapiens mRNA, which shows an m(1)A/A ratio of ∼0.02%. We develop the m(1)A-ID-seq technique, based on m(1)A immunoprec...

journal_title：Nature chemical biology

authors： Li X,Xiong X,Wang K,Wang L,Shu X,Ma S,Yi C

更新日期：2016-05-01 00:00:00

abstract：:Sulfoquinovose is produced by photosynthetic organisms at a rate of 10(10) tons per annum and is degraded by bacteria as a source of carbon and sulfur. We have identified Escherichia coli YihQ as the first dedicated sulfoquinovosidase and the gateway enzyme to sulfoglycolytic pathways. Structural and mutagenesis studi...

journal_title：Nature chemical biology

authors： Speciale G,Jin Y,Davies GJ,Williams SJ,Goddard-Borger ED

更新日期：2016-04-01 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：:Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity ...

journal_title：Nature chemical biology

authors： Rees MG,Seashore-Ludlow B,Cheah JH,Adams DJ,Price EV,Gill S,Javaid S,Coletti ME,Jones VL,Bodycombe NE,Soule CK,Alexander B,Li A,Montgomery P,Kotz JD,Hon CS,Munoz B,Liefeld T,Dančík V,Haber DA,Clish CB,Bittker JA

更新日期：2016-02-01 00:00:00

abstract：:The active site of [NiFe] hydrogenases contains a strictly conserved arginine that suspends a guanidine nitrogen atom <4.5 Å above the nickel and iron atoms. The guanidine headgroup interacts with the side chains of two conserved aspartic acid residues to complete an outer-shell canopy that has thus far proved intract...

journal_title：Nature chemical biology

authors： Evans RM,Brooke EJ,Wehlin SA,Nomerotskaia E,Sargent F,Carr SB,Phillips SE,Armstrong FA

更新日期：2016-01-01 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：:Mitochondrial electron transport drives ATP synthesis but also generates reactive oxygen species, which are both cellular signals and damaging oxidants. Superoxide production by respiratory complex III is implicated in diverse signaling events and pathologies, but its role remains controversial. Using high-throughput ...

journal_title：Nature chemical biology

authors： Orr AL,Vargas L,Turk CN,Baaten JE,Matzen JT,Dardov VJ,Attle SJ,Li J,Quackenbush DC,Goncalves RL,Perevoshchikova IV,Petrassi HM,Meeusen SL,Ainscow EK,Brand MD

更新日期：2015-11-01 00:00:00

abstract：:Excessive aggregation of proteins has a major impact on cell fate and is a hallmark of amyloid diseases in humans. To resolve insoluble deposits and to maintain protein homeostasis, all cells use dedicated protein disaggregation, protein folding and protein degradation factors. Despite intense recent research, the und...

journal_title：Nature chemical biology

authors： Poepsel S,Sprengel A,Sacca B,Kaschani F,Kaiser M,Gatsogiannis C,Raunser S,Clausen T,Ehrmann M

更新日期：2015-11-01 00:00:00

abstract：:In eukaryotes, cytosolic monothiol glutaredoxins are proteins implicated in intracellular iron trafficking and sensing via their bound [2Fe-2S] clusters. We define a new role of human cytosolic monothiol glutaredoxin-3 (GRX3) in transferring its [2Fe-2S] clusters to human anamorsin, a physical and functional protein p...

journal_title：Nature chemical biology

authors： Banci L,Ciofi-Baffoni S,Gajda K,Muzzioli R,Peruzzini R,Winkelmann J

更新日期：2015-10-01 00:00:00

abstract：:The P1B-ATPases, which couple cation transport across membranes to ATP hydrolysis, are central to metal homeostasis in all organisms. An important feature of P1B-ATPases is the presence of soluble metal binding domains (MBDs) that regulate transport activity. Only one type of MBD has been characterized extensively, bu...

journal_title：Nature chemical biology

authors： Smith AT,Barupala D,Stemmler TL,Rosenzweig AC

更新日期：2015-09-01 00:00:00

abstract：:5-Formylcytosine (5fC) is a rare base found in mammalian DNA and thought to be involved in active DNA demethylation. Here, we show that developmental dynamics of 5fC levels in mouse DNA differ from those of 5-hydroxymethylcytosine (5hmC), and using stable isotope labeling in vivo, we show that 5fC can be a stable DNA ...

journal_title：Nature chemical biology

authors： Bachman M,Uribe-Lewis S,Yang X,Burgess HE,Iurlaro M,Reik W,Murrell A,Balasubramanian S

更新日期：2015-08-01 00:00:00

abstract：:Serine phosphorylation is a key post-translational modification that regulates diverse biological processes. Powerful analytical methods have identified thousands of phosphorylation sites, but many of their functions remain to be deciphered. A key to understanding the function of protein phosphorylation is access to p...

journal_title：Nature chemical biology

authors： Rogerson DT,Sachdeva A,Wang K,Haq T,Kazlauskaite A,Hancock SM,Huguenin-Dezot N,Muqit MM,Fry AM,Bayliss R,Chin JW

更新日期：2015-07-01 00:00:00

abstract：:Benzylisoquinoline alkaloids (BIAs) are a diverse family of plant-specialized metabolites that include the pharmaceuticals codeine and morphine and their derivatives. Microbial synthesis of BIAs holds promise as an alternative to traditional crop-based manufacturing. Here we demonstrate the production of the key BIA i...

journal_title：Nature chemical biology

authors： DeLoache WC,Russ ZN,Narcross L,Gonzales AM,Martin VJ,Dueber JE

更新日期：2015-07-01 00:00:00

abstract：:The chemical species involved in H2S signaling remain elusive despite the profound and pleiotropic physiological effects elicited by this molecule. The dominant candidate mechanism for sulfide signaling is persulfidation of target proteins. However, the relatively poor reactivity of H2S toward oxidized thiols, such as...

journal_title：Nature chemical biology

authors： Mishanina TV,Libiad M,Banerjee R

更新日期：2015-07-01 00:00:00

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：:Lipid rafts in plasma membranes have emerged as possible platforms for the entry of HIV and other viruses into cells. However, little is known about how lipid phase heterogeneity contributes to viral entry because of the fine-grained and still poorly understood complexity of biological membranes. We used model systems...

journal_title：Nature chemical biology

authors： Yang ST,Kiessling V,Simmons JA,White JM,Tamm LK

更新日期：2015-06-01 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：:Trafficking and sorting of membrane-anchored Ras GTPases are regulated by partitioning between distinct membrane domains. Here, in vitro experiments and microscopic molecular theory reveal membrane curvature as a new modulator of N-Ras lipid anchor and palmitoyl chain partitioning. Membrane curvature was essential for...

journal_title：Nature chemical biology

authors： Larsen JB,Jensen MB,Bhatia VK,Pedersen SL,Bjørnholm T,Iversen L,Uline M,Szleifer I,Jensen KJ,Hatzakis NS,Stamou D

更新日期：2015-03-01 00:00:00

abstract：:Identifying the interaction partners of noncoding RNAs is essential for elucidating their functions. We have developed an approach, termed microRNA crosslinking and immunoprecipitation (miR-CLIP), using pre-miRNAs modified with psoralen and biotin to capture their targets in cells. Photo-crosslinking and Argonaute 2 i...

journal_title：Nature chemical biology

authors： Imig J,Brunschweiger A,Brümmer A,Guennewig B,Mittal N,Kishore S,Tsikrika P,Gerber AP,Zavolan M,Hall J

更新日期：2015-02-01 00:00:00

abstract：:Secondary structure refolding is a key event in biology as it modulates the conformation of many proteins in the cell, generating functional or aberrant states. The crystal structures of mannosyltransferase PimA reveal an exceptional flexibility of the protein along the catalytic cycle, including β-strand-to-α-helix a...

journal_title：Nature chemical biology

authors： Giganti D,Albesa-Jové D,Urresti S,Rodrigo-Unzueta A,Martínez MA,Comino N,Barilone N,Bellinzoni M,Chenal A,Guerin ME,Alzari PM

更新日期：2015-01-01 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：:The inability of cells to properly fold, modify and assemble secretory and transmembrane proteins leads to accumulation of misfolded proteins in the endoplasmic reticulum (ER). Under these conditions of 'ER stress', cell survival depends on homeostatic benefits from an intracellular signaling pathway called the unfold...

journal_title：Nature chemical biology

authors： Maly DJ,Papa FR

更新日期：2014-11-01 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：:Regio- and stereospecific incorporation of a halogen atom to an unactivated sp(3) carbon in a freestanding molecule is a challenging transformation that is currently missing in the inventory of enzyme-mediated reactions. Here we report what is to our knowledge the first example of a nonheme iron enzyme (WelO5) in the ...

journal_title：Nature chemical biology

authors： Hillwig ML,Liu X

更新日期：2014-11-01 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：: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：:The potential utility of synthetic macrocycles (MCs) as drugs, particularly against low-druggability targets such as protein-protein interactions, has been widely discussed. There is little information, however, to guide the design of MCs for good target protein-binding activity or bioavailability. To address this kno...

journal_title：Nature chemical biology

authors： Villar EA,Beglov D,Chennamadhavuni S,Porco JA Jr,Kozakov D,Vajda S,Whitty A

更新日期：2014-09-01 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：:Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have distinct clinical features but a common pathology--cytoplasmic inclusions rich in transactive response element DNA-binding protein of 43 kDa (TDP43). Rare TDP43 mutations cause ALS or FTD, but abnormal TDP43 levels and localization may cause di...

journal_title：Nature chemical biology

authors： Barmada SJ,Serio A,Arjun A,Bilican B,Daub A,Ando DM,Tsvetkov A,Pleiss M,Li X,Peisach D,Shaw C,Chandran S,Finkbeiner S

更新日期：2014-08-01 00:00:00

abstract：:The Watson-Crick base pairs between the 3'-terminal end of tRNAs and ribosomal RNA in the peptidyl transferase center are universally conserved. Here, we report that the introduction of compensatory mutations to Escherichia coli RNAs in this site leads to an orthogonal system independent of the wild-type counterpart, ...

journal_title：Nature chemical biology

authors： Terasaka N,Hayashi G,Katoh T,Suga H

更新日期：2014-07-01 00:00:00

abstract：:Methods for imaging and tracking single molecules conjugated with fluorescent probes, called single-molecule tracking (SMT), are now providing researchers with the unprecedented ability to directly observe molecular behaviors and interactions in living cells. Current SMT methods are achieving almost the ultimate spati...

journal_title：Nature chemical biology

authors： Kusumi A,Tsunoyama TA,Hirosawa KM,Kasai RS,Fujiwara TK

更新日期：2014-07-01 00:00:00

abstract：:Despite the remarkable versatility displayed by flavin-dependent monooxygenases (FMOs) in natural product biosynthesis, one notably missing activity is the oxidative generation of carbonate functional groups. We describe a multifunctional Baeyer-Villiger monooxygenase, CcsB, which catalyzes the formation of an in-line...

journal_title：Nature chemical biology

authors： Hu Y,Dietrich D,Xu W,Patel A,Thuss JA,Wang J,Yin WB,Qiao K,Houk KN,Vederas JC,Tang Y

更新日期：2014-07-01 00:00:00

abstract：:The serotonin6 receptor (5-HT6R) is a promising target for treating cognitive deficits of schizophrenia often linked to alterations of neuronal development. This receptor controls neurodevelopmental processes, but the signaling mechanisms involved remain poorly understood. Using a proteomic strategy, we show that 5-HT...

journal_title：Nature chemical biology

authors： Duhr F,Déléris P,Raynaud F,Séveno M,Morisset-Lopez S,Mannoury la Cour C,Millan MJ,Bockaert J,Marin P,Chaumont-Dubel S

更新日期：2014-07-01 00:00:00

abstract：:Natural enzymes have evolved to perform their cellular functions under complex selective pressures, which often require their catalytic activities to be regulated by other proteins. We contrasted a natural enzyme, LovD, which acts on a protein-bound (LovF) acyl substrate, with a laboratory-generated variant that was t...

journal_title：Nature chemical biology

authors： Jiménez-Osés G,Osuna S,Gao X,Sawaya MR,Gilson L,Collier SJ,Huisman GW,Yeates TO,Tang Y,Houk KN

更新日期：2014-06-01 00:00:00

abstract：:Gut microbiota is found in virtually any metazoan, from invertebrates to vertebrates. It has long been believed that gut microbiota, more specifically, the activity of the microbiome and its metabolic products, directly influence a variety of aspects in metazoan physiology. However, the exact molecular relationship am...

journal_title：Nature chemical biology

authors： Lee WJ,Hase K

更新日期：2014-06-01 00:00:00

abstract：:Specific chemicals can prime the plant immune system for augmented defense. β-aminobutyric acid (BABA) is a priming agent that provides broad-spectrum disease protection. However, BABA also suppresses plant growth when applied in high doses, which has hampered its application as a crop defense activator. Here we descr...

journal_title：Nature chemical biology

authors： Luna E,van Hulten M,Zhang Y,Berkowitz O,López A,Pétriacq P,Sellwood MA,Chen B,Burrell M,van de Meene A,Pieterse CM,Flors V,Ton J

更新日期：2014-06-01 00:00:00