Chemical proteomics reveals ADP-ribosylation of small GTPases during oxidative stress.

abstract：:Designing selective inhibitors of proteases has proven problematic, in part because pharmacophores that confer potency exploit the conserved catalytic apparatus. We developed a fundamentally different approach by designing irreversible inhibitors that target noncatalytic cysteines that are structurally unique to a tar...

journal_title：Nature chemical biology

authors： Hagel M,Niu D,St Martin T,Sheets MP,Qiao L,Bernard H,Karp RM,Zhu Z,Labenski MT,Chaturvedi P,Nacht M,Westlin WF,Petter RC,Singh J

更新日期：2011-01-01 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：: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：: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：:Combination antiretroviral therapy has transformed HIV-1 infection, once a fatal illness, into a manageable chronic condition. Drug resistance, severe side effects and treatment noncompliance bring challenges to combination antiretroviral therapy implementation in clinical settings and indicate the need for additional...

journal_title：Nature chemical biology

authors： Xiao T,Frey G,Fu Q,Lavine CL,Scott DA,Seaman MS,Chou JJ,Chen B

更新日期：2020-05-01 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：: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：:Nature uses a variety of tools to mediate the flow of information in cells, many of which control distances between key biomacromolecules. Researchers have thus generated compounds whose activities stem from interactions with two (or more) proteins simultaneously. In this Perspective, we describe how these 'bifunction...

journal_title：Nature chemical biology

authors： Gerry CJ,Schreiber SL

更新日期：2020-04-01 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：:Virtually all cells in the body have an intracellular clockwork based on a negative feedback mechanism. The circadian timekeeping system in mammals is a hierarchical multi-oscillator network, with the suprachiasmatic nuclei (SCN) acting as the central pacemaker. The SCN synchronizes to daily light-dark cycles and coor...

journal_title：Nature chemical biology

authors： Liu AC,Lewis WG,Kay SA

更新日期：2007-10-01 00:00:00

abstract：:Gentamicin B (GB), a valuable starting material for the preparation of the semisynthetic aminoglycoside antibiotic isepamicin, is produced in trace amounts by the wild-type Micromonospora echinospora. Though the biosynthetic pathway to GB has remained obscure for decades, we have now identified three hidden pathways t...

journal_title：Nature chemical biology

authors： Ban YH,Song MC,Hwang JY,Shin HL,Kim HJ,Hong SK,Lee NJ,Park JW,Cha SS,Liu HW,Yoon YJ

更新日期：2019-03-01 00:00:00

abstract：:Plants have recently moved into the spotlight owing to the growing realization that the world needs solutions to energy and food production that are sustainable and environmentally sound. Iron, copper and zinc are essential for plant growth and development, yet the same properties that make these transition metals ind...

journal_title：Nature chemical biology

authors： Palmer CM,Guerinot ML

更新日期：2009-05-01 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：: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：: ...

journal_title：Nature chemical biology

authors： Singh Gautam AK,Matouschek A

更新日期：2019-03-01 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：: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：:The molecular forces that drive structural transitions between the open and closed states of channels and transporters are not well understood. The gate of the OmpA channel is formed by the central Glu52-Arg138 salt bridge, which can open to form alternate ion pairs with Lys82 and Glu128. To gain deeper insight into t...

journal_title：Nature chemical biology

authors： Hong H,Szabo G,Tamm LK

更新日期：2006-11-01 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：: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：: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：: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：: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：:Foldamers are sequence-specific oligomers akin to peptides, proteins and oligonucleotides that fold into well-defined three-dimensional structures. They offer the chemical biologist a broad pallet of building blocks for the construction of molecules that test and extend our understanding of protein folding and functio...

journal_title：Nature chemical biology

authors： Goodman CM,Choi S,Shandler S,DeGrado WF

更新日期：2007-05-01 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：: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：: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：: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：: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

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