Optogenetic control of kinetochore function.

abstract：:Subtilosin A is a 35-residue, ribosomally synthesized bacteriocin encoded by the sbo-alb operon of Bacillus subtilis. It is composed of a head-to-tail circular peptide backbone that is additionally restrained by three unusual thioether bonds between three cysteines and the α-carbon of one threonine and two phenylalani...

journal_title：Nature chemical biology

authors： Flühe L,Knappe TA,Gattner MJ,Schäfer A,Burghaus O,Linne U,Marahiel MA

更新日期：2012-02-26 00:00:00

abstract：:The resistance of Caenorhabditis elegans to pharmacological perturbation limits its use as a screening tool for novel small bioactive molecules. One strategy to improve the hit rate of small-molecule screens is to preselect molecules that have an increased likelihood of reaching their target in the worm. To learn whic...

journal_title：Nature chemical biology

authors： Burns AR,Wallace IM,Wildenhain J,Tyers M,Giaever G,Bader GD,Nislow C,Cutler SR,Roy PJ

更新日期：2010-07-01 00:00:00

abstract：:Studies of gene function and molecular mechanisms in Plasmodium falciparum are hampered by difficulties in characterizing and measuring phenotypic differences between individual parasites. We screened seven parasite lines for differences in responses to 1,279 bioactive chemicals. Hundreds of compounds were active in i...

journal_title：Nature chemical biology

authors： Yuan J,Johnson RL,Huang R,Wichterman J,Jiang H,Hayton K,Fidock DA,Wellems TE,Inglese J,Austin CP,Su XZ

更新日期：2009-10-01 00:00:00

abstract：:Propofol is the most important intravenous general anesthetic in current clinical use. It acts by potentiating GABAA (γ-aminobutyric acid type A) receptors, but where it binds to this receptor is not known and has been a matter of some debate. We synthesized a new propofol analog photolabeling reagent whose biological...

journal_title：Nature chemical biology

authors： Yip GM,Chen ZW,Edge CJ,Smith EH,Dickinson R,Hohenester E,Townsend RR,Fuchs K,Sieghart W,Evers AS,Franks NP

更新日期：2013-11-01 00:00:00

abstract：:The chemical scaffolds from which screening libraries are built have strong influence on the libraries' utility for screening campaigns. Here we present analysis of the scaffold composition of several types of commercially available screening collections and compare those compositions to those of drugs and drug candid...

journal_title：Nature chemical biology

authors： Shelat AA,Guy RK

更新日期：2007-08-01 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：: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：:We identify an Arabidopsis pyridoxal-phosphate-dependent aminotransferase, VAS1, whose loss-of-function simultaneously increases amounts of the phytohormone auxin and the ethylene precursor 1-aminocyclopropane-1-carboxylate. VAS1 uses the ethylene biosynthetic intermediate methionine as an amino donor and the auxin bi...

journal_title：Nature chemical biology

authors： Zheng Z,Guo Y,Novák O,Dai X,Zhao Y,Ljung K,Noel JP,Chory J

更新日期：2013-04-01 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：:Enzymes that use the cofactor thiamin diphosphate (ThDP, 1), the biologically active form of vitamin B(1), are involved in numerous metabolic pathways in all organisms. Although a theory of the cofactor's underlying reaction mechanism has been established over the last five decades, the three-dimensional structures of...

journal_title：Nature chemical biology

authors： Wille G,Meyer D,Steinmetz A,Hinze E,Golbik R,Tittmann K

更新日期：2006-06-01 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：: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：:The simultaneous observation of interdependent reactions within different phases as catalyzed by membrane-bound enzymes is still a challenging task. One such enzyme, the Escherichia coli integral membrane protein diacylglycerol kinase (DGK), is a key player in lipid regulation. It catalyzes the generation of phosphati...

journal_title：Nature chemical biology

authors： Ullrich SJ,Hellmich UA,Ullrich S,Glaubitz C

更新日期：2011-05-01 00:00:00

abstract：:N6-Methyladenosine (m6A) RNA modification is present in messenger RNAs (mRNA), ribosomal RNAs (rRNA), and spliceosomal RNAs (snRNA) in humans. Although mRNA m6A modifications have been extensively studied and shown to play critical roles in many cellular processes, the identity of m6A methyltransferases for rRNAs and ...

journal_title：Nature chemical biology

authors： Ma H,Wang X,Cai J,Dai Q,Natchiar SK,Lv R,Chen K,Lu Z,Chen H,Shi YG,Lan F,Fan J,Klaholz BP,Pan T,Shi Y,He C

更新日期：2019-01-01 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：: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：:Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vi...

journal_title：Nature chemical biology

authors： Ferguson FM,Nabet B,Raghavan S,Liu Y,Leggett AL,Kuljanin M,Kalekar RL,Yang A,He S,Wang J,Ng RWS,Sulahian R,Li L,Poulin EJ,Huang L,Koren J,Dieguez-Martinez N,Espinosa S,Zeng Z,Corona CR,Vasta JD,Ohi R,Sim T,K

更新日期：2020-06-01 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：:Kinase inhibitors are important cancer drugs, but they tend to display limited target specificity, and their target profiles are often challenging to rationalize in terms of molecular mechanism. Here we report that the clinical kinase inhibitor bosutinib recognizes its kinase targets by engaging a pair of conserved st...

journal_title：Nature chemical biology

authors： Levinson NM,Boxer SG

更新日期：2014-02-01 00:00:00

abstract：:Small molecules stabilize specific protein conformations from a larger ensemble, enabling molecular switches that control diverse cellular functions. We show here that the converse also holds true: the conformational state of the estrogen receptor can direct distinct orientations of the bound ligand. 'Gain-of-alloster...

journal_title：Nature chemical biology

authors： Bruning JB,Parent AA,Gil G,Zhao M,Nowak J,Pace MC,Smith CL,Afonine PV,Adams PD,Katzenellenbogen JA,Nettles KW

更新日期：2010-11-01 00:00:00

abstract：:Vertebrate vision is initiated by photoisomerization of the visual pigment chromophore 11-cis-retinal and is maintained by continuous regeneration of this retinoid through a series of reactions termed the retinoid cycle. However, toxic side reaction products, especially those involving reactive aldehyde groups of the ...

journal_title：Nature chemical biology

authors： Maeda A,Golczak M,Chen Y,Okano K,Kohno H,Shiose S,Ishikawa K,Harte W,Palczewska G,Maeda T,Palczewski K

更新日期：2011-12-25 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：:The ykkC family of bacterial riboswitches combines several widespread classes that have similar secondary structures and consensus motifs but control different genes in response to different cellular metabolites. Here we report the crystal structures of two distinct ykkC riboswitches specifically bound to their cognat...

journal_title：Nature chemical biology

authors： Peselis A,Serganov A

更新日期：2018-09-01 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：:Lysine riboswitches are bacterial RNA structures that sense the concentration of lysine and regulate the expression of lysine biosynthesis and transport genes. Members of this riboswitch class are found in the 5' untranslated region of messenger RNAs, where they form highly selective receptors for lysine. Lysine bindi...

journal_title：Nature chemical biology

authors： Blount KF,Wang JX,Lim J,Sudarsan N,Breaker RR

更新日期：2007-01-01 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：: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：:The function of many biologically active molecules requires the presence of carbon-nitrogen bonds in strategic positions. The biosynthetic pathways leading to such bonds can be bypassed through chemical synthesis to synthesize natural products more efficiently and also to generate the molecular diversity unavailable i...

journal_title：Nature chemical biology

authors： Hili R,Yudin AK

更新日期：2006-06-01 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：:Bile salt hydrolase (BSH) enzymes are widely expressed by human gut bacteria and catalyze the gateway reaction leading to secondary bile acid formation. Bile acids regulate key metabolic and immune processes by binding to host receptors. There is an unmet need for a potent tool to inhibit BSHs across all gut bacteria ...

journal_title：Nature chemical biology

authors： Adhikari AA,Seegar TCM,Ficarro SB,McCurry MD,Ramachandran D,Yao L,Chaudhari SN,Ndousse-Fetter S,Banks AS,Marto JA,Blacklow SC,Devlin AS

更新日期：2020-03-01 00:00:00