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：:Concatenation of engineered biocatalysts into multistep pathways markedly increases their utility, but the development of generalizable assembly methods remains a major challenge. Herein we evaluate 'bioretrosynthesis', which is an application of the retrograde evolution hypothesis, for biosynthetic pathway constructi...

journal_title：Nature chemical biology

authors： Birmingham WR,Starbird CA,Panosian TD,Nannemann DP,Iverson TM,Bachmann BO

更新日期：2014-05-01 00:00:00

abstract：:Bacteria are thought to cope with fluctuating environmental solute concentrations primarily by adjusting the osmolality of their cytoplasm. To obtain insights into the underlying metabolic adaptations, we analyzed the global metabolic response of Escherichia coli to sustained hyperosmotic stress using nontargeted mass...

journal_title：Nature chemical biology

authors： Sévin DC,Sauer U

更新日期：2014-04-01 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：: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：: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：:Here we identify the amino acid transporter AnsP1 as the unique aspartate importer in the human pathogen Mycobacterium tuberculosis. Metabolomic analysis of a mutant with an inactive AnsP1 revealed that the transporter is essential for M. tuberculosis to assimilate nitrogen from aspartate. Virulence of the AnsP1 mutan...

journal_title：Nature chemical biology

authors： Gouzy A,Larrouy-Maumus G,Wu TD,Peixoto A,Levillain F,Lugo-Villarino G,Guerquin-Kern JL,de Carvalho LP,Poquet Y,Neyrolles O

更新日期：2013-11-01 00:00:00

abstract：:We report a salvage pathway in Gram-negative bacteria that bypasses de novo biosynthesis of UDP N-acetylmuramic acid (UDP-MurNAc), the first committed peptidoglycan precursor, and thus provides a rationale for intrinsic fosfomycin resistance. The anomeric sugar kinase AmgK and the MurNAc α-1-phosphate uridylyl transfe...

journal_title：Nature chemical biology

authors： Gisin J,Schneider A,Nägele B,Borisova M,Mayer C

更新日期：2013-08-01 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：:Nontranslational functions of vertebrate aminoacyl tRNA synthetases (aaRSs), which catalyze the production of aminoacyl-tRNAs for protein synthesis, have recently been discovered. Although these new functions were thought to be 'moonlighting activities', many are as critical for cellular homeostasis as their activity ...

journal_title：Nature chemical biology

authors： Guo M,Schimmel P

更新日期：2013-03-01 00:00:00

abstract：:Improving the control of energy homeostasis can lower cardiovascular risk in metabolically compromised individuals. To identify new regulators of whole-body energy control, we conducted a high-throughput screen in transgenic reporter zebrafish for small molecules that modulate the expression of the fasting-inducible g...

journal_title：Nature chemical biology

authors： Gut P,Baeza-Raja B,Andersson O,Hasenkamp L,Hsiao J,Hesselson D,Akassoglou K,Verdin E,Hirschey MD,Stainier DY

更新日期：2013-02-01 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：:The endocannabinoid 2-arachidonoylglycerol (2-AG) is biosynthesized by diacylglycerol lipases DAGLα and DAGLβ. Chemical probes to perturb DAGLs are needed to characterize endocannabinoid function in biological processes. Here we report a series of 1,2,3-triazole urea inhibitors, along with paired negative-control and ...

journal_title：Nature chemical biology

authors： Hsu KL,Tsuboi K,Adibekian A,Pugh H,Masuda K,Cravatt BF

更新日期：2012-12-01 00:00:00

abstract：:Occurrence of the BCR-ABL(T315I) gatekeeper mutation is among the most pressing challenges in the therapy of chronic myeloid leukemia (CML). Several BCR-ABL inhibitors have multiple targets and pleiotropic effects that could be exploited for their synergistic potential. Testing combinations of such kinase inhibitors i...

journal_title：Nature chemical biology

authors： Winter GE,Rix U,Carlson SM,Gleixner KV,Grebien F,Gridling M,Müller AC,Breitwieser FP,Bilban M,Colinge J,Valent P,Bennett KL,White FM,Superti-Furga G

更新日期：2012-11-01 00:00:00

abstract：:The streptothricin (ST) antibiotics, produced by Streptomyces bacteria, contain L-β-lysine ((3S)-3,6-diaminohexanoic acid) oligopeptides as pendant chains. Here we describe three unusual nonribosomal peptide synthetases (NRPSs) involved in ST biosynthesis: ORF 5 (a stand-alone adenylation (A) domain), ORF 18 (containi...

journal_title：Nature chemical biology

authors： Maruyama C,Toyoda J,Kato Y,Izumikawa M,Takagi M,Shin-ya K,Katano H,Utagawa T,Hamano Y

更新日期：2012-09-01 00:00:00

abstract：:Single-molecule observations reveal that lipid- and protein-based interactions jointly contribute to the interactions among glycosylphosphatidylinositol-anchored proteins in membranes. Understanding these interactions will help to refine long-evolving (and still debated) models of 'raft' domains in biological membrane...

journal_title：Nature chemical biology

authors： Silvius JR

更新日期：2012-09-01 00:00:00

abstract：:Phenylketonuria (PKU) is characterized by phenylalanine accumulation and progressive mental retardation caused by an unknown mechanism. We demonstrate that at pathological concentrations, phenylalanine self-assembles into fibrils with amyloid-like morphology and well-ordered electron diffraction. These assemblies are ...

journal_title：Nature chemical biology

authors： Adler-Abramovich L,Vaks L,Carny O,Trudler D,Magno A,Caflisch A,Frenkel D,Gazit E

更新日期：2012-08-01 00:00:00

abstract：:Despite the fundamental roles of sialyl- and fucosyltransferases in mammalian physiology, there are few pharmacological tools to manipulate their function in a cellular setting. Although fluorinated analogs of the donor substrates are well-established transition state inhibitors of these enzymes, they are not membrane...

journal_title：Nature chemical biology

authors： Rillahan CD,Antonopoulos A,Lefort CT,Sonon R,Azadi P,Ley K,Dell A,Haslam SM,Paulson JC

更新日期：2012-07-01 00:00:00

abstract：:Receptor-mediated endocytosis is an integral part of signal transduction as it mediates signal attenuation and provides spatial and temporal dimensions to signaling events. One of the best-studied leucine-rich repeat receptor-like kinases in plants, BRASSINOSTEROID INSENSITIVE 1 (BRI1), perceives its ligand, the brass...

journal_title：Nature chemical biology

authors： Irani NG,Di Rubbo S,Mylle E,Van den Begin J,Schneider-Pizoń J,Hniliková J,Šíša M,Buyst D,Vilarrasa-Blasi J,Szatmári AM,Van Damme D,Mishev K,Codreanu MC,Kohout L,Strnad M,Caño-Delgado AI,Friml J,Madder A,Russinova E

更新日期：2012-05-06 00:00:00

abstract：:Thiazole/oxazole-modified microcins (TOMMs) encompass a recently defined class of ribosomally synthesized natural products with a diverse set of biological activities. Although TOMM biosynthesis has been investigated for over a decade, the mechanism of heterocycle formation by the synthetase enzymes remains poorly und...

journal_title：Nature chemical biology

authors： Dunbar KL,Melby JO,Mitchell DA

更新日期：2012-04-22 00:00:00

abstract：:We describe a new technology for recruiting specific proteins to RNA through selective recognition of heteroduplexes formed with chemically modified antisense oligonucleotides (ASOs). Typically, ASOs function by hybridizing to their RNA targets and blocking the binding of single-stranded RNA-binding proteins. Unexpect...

journal_title：Nature chemical biology

authors： Rigo F,Hua Y,Chun SJ,Prakash TP,Krainer AR,Bennett CF

更新日期：2012-04-15 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：: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：:Guanine-rich DNA sequences that can adopt non-Watson-Crick structures in vitro are prevalent in the human genome. Whether such structures normally exist in mammalian cells has, however, been the subject of active research for decades. Here we show that the G-quadruplex-interacting drug pyridostatin promotes growth arr...

journal_title：Nature chemical biology

authors： Rodriguez R,Miller KM,Forment JV,Bradshaw CR,Nikan M,Britton S,Oelschlaegel T,Xhemalce B,Balasubramanian S,Jackson SP

更新日期：2012-02-05 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：:Protein serine-threonine kinase casein kinase II (CK2) is involved in a myriad of cellular processes including cell growth and proliferation through its phosphorylation of hundreds of substrates, yet how CK2 function is regulated is poorly understood. Here we report that the CK2 catalytic subunit CK2α is modified by O...

journal_title：Nature chemical biology

authors： Tarrant MK,Rho HS,Xie Z,Jiang YL,Gross C,Culhane JC,Yan G,Qian J,Ichikawa Y,Matsuoka T,Zachara N,Etzkorn FA,Hart GW,Jeong JS,Blackshaw S,Zhu H,Cole PA

更新日期：2012-01-22 00:00:00

abstract：:Signal transduction, regulatory processes and pharmaceutical responses are highly dependent upon ligand residence times. Gaining insight into how physical factors influence residence times (1/k(off)) should enhance our ability to manipulate biological interactions. We report experiments that yield structural insight i...

journal_title：Nature chemical biology

authors： Carroll MJ,Mauldin RV,Gromova AV,Singleton SF,Collins EJ,Lee AL

更新日期：2012-01-15 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：:The eukaryotic replicative DNA polymerases (Pol α, δ and ɛ) and the major DNA mutagenesis enzyme Pol ζ contain two conserved cysteine-rich metal-binding motifs (CysA and CysB) in the C-terminal domain (CTD) of their catalytic subunits. Here we demonstrate by in vivo and in vitro approaches the presence of an essential...

journal_title：Nature chemical biology

authors： Netz DJ,Stith CM,Stümpfig M,Köpf G,Vogel D,Genau HM,Stodola JL,Lill R,Burgers PM,Pierik AJ

更新日期：2011-11-27 00:00:00

abstract：:Although metabolic networks have been reconstructed on a genome scale, the corresponding reconstruction and integration of governing transcriptional regulatory networks has not been fully achieved. Here we reconstruct such an integrated network for amino acid metabolism in Escherichia coli. Analysis of ChIP-chip and g...

journal_title：Nature chemical biology

authors： Cho BK,Federowicz S,Park YS,Zengler K,Palsson BØ

更新日期：2011-11-13 00:00:00

abstract：:Polyglutamine (polyQ) stretches exceeding a threshold length confer a toxic function to proteins that contain them and cause at least nine neurological disorders. The basis for this toxicity threshold is unclear. Although polyQ expansions render proteins prone to aggregate into inclusion bodies, this may be a neuronal...

journal_title：Nature chemical biology

authors： Miller J,Arrasate M,Brooks E,Libeu CP,Legleiter J,Hatters D,Curtis J,Cheung K,Krishnan P,Mitra S,Widjaja K,Shaby BA,Lotz GP,Newhouse Y,Mitchell EJ,Osmand A,Gray M,Thulasiramin V,Saudou F,Segal M,Yang XW,Masliah

更新日期：2011-10-30 00:00:00

abstract：:We report here that fat mass and obesity-associated protein (FTO) has efficient oxidative demethylation activity targeting the abundant N6-methyladenosine (m(6)A) residues in RNA in vitro. FTO knockdown with siRNA led to increased amounts of m(6)A in mRNA, whereas overexpression of FTO resulted in decreased amounts of...

journal_title：Nature chemical biology

authors： Jia G,Fu Y,Zhao X,Dai Q,Zheng G,Yang Y,Yi C,Lindahl T,Pan T,Yang YG,He C

更新日期：2011-10-16 00:00:00

abstract：:Proteoglycans are complex glycoconjugates that regulate critical biological pathways in all higher organisms. Bikunin, the simplest proteoglycan, with a single glycosaminoglycan chain, is a serine protease inhibitor used to treat acute pancreatitis. Unlike nucleic acids and proteins, whose synthesis is template driven...

journal_title：Nature chemical biology

authors： Ly M,Leach FE 3rd,Laremore TN,Toida T,Amster IJ,Linhardt RJ

更新日期：2011-10-09 00:00:00

abstract：:We report that simple glycoside donors can drastically shift the equilibria of glycosyltransferase-catalyzed reactions, transforming NDP-sugar formation from an endothermic to an exothermic process. To demonstrate the utility of this thermodynamic adaptability, we highlight the glycosyltransferase-catalyzed synthesis ...

journal_title：Nature chemical biology

authors： Gantt RW,Peltier-Pain P,Cournoyer WJ,Thorson JS

更新日期：2011-08-21 00:00:00

abstract：:In response to decreasing Ca2+ levels in the endoplasmic reticulum, STIM proteins couple with Orai channels in the plasma membrane, leading to Ca2+ influx into the cell. In addition to Ca2+-related endoplasmic reticulum stress, STIM proteins are emerging as general stress sensors that react to multiple stress signals ...

journal_title：Nature chemical biology

authors： Soboloff J,Madesh M,Gill DL

更新日期：2011-07-18 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：: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：:We document a new dimension of surface recognition in which communication is controlled through the collective behavior of lipids. Membrane cholesterol induces a tilt in glycolipid receptor headgroup, resulting in loss of access for ligand binding. This property appears to organize erythrocyte blood group presentation...

journal_title：Nature chemical biology

authors： Lingwood D,Binnington B,Róg T,Vattulainen I,Grzybek M,Coskun U,Lingwood CA,Simons K

更新日期：2011-05-01 00:00:00

abstract：:Glycosyltransferases are ubiquitous enzymes that catalyze the assembly of glycoconjugates throughout all kingdoms of nature. A long-standing problem is the rational design of probes that can be used to manipulate glycosyltransferase activity in cells and tissues. Here we describe the rational design and synthesis of a...

journal_title：Nature chemical biology

authors： Gloster TM,Zandberg WF,Heinonen JE,Shen DL,Deng L,Vocadlo DJ

更新日期：2011-03-01 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