Small-molecule activation of procaspase-3 to caspase-3 as a personalized anticancer strategy.

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：:Mammals that degrade uric acid are not affected by gout or urate kidney stones. It is not fully understood how they convert uric acid into the much more soluble allantoin. Until recently, it had long been thought that urate oxidase was the only enzyme responsible for this conversion. However, detailed studies of the m...

journal_title：Nature chemical biology

authors： Ramazzina I,Folli C,Secchi A,Berni R,Percudani R

更新日期：2006-03-01 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：:Drug discovery resources in academia and industry are not used efficiently, to the detriment of industry and society. Duplication could be reduced, and productivity could be increased, by performing basic biology and clinical proofs of concept within open access industry-academia partnerships. Chemical biologists coul...

journal_title：Nature chemical biology

authors： Edwards AM,Bountra C,Kerr DJ,Willson TM

更新日期：2009-07-01 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：:ADP-ribosylation (ADPr) is a biologically and clinically important post-translational modification, but little is known about the amino acids it targets on cellular proteins. Here we present a proteomic approach for direct in vivo identification and quantification of ADPr sites on histones. We have identified 12 uniqu...

journal_title：Nature chemical biology

authors： Leidecker O,Bonfiglio JJ,Colby T,Zhang Q,Atanassov I,Zaja R,Palazzo L,Stockum A,Ahel I,Matic I

更新日期：2016-12-01 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：: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：:Targeted protein degradation via small-molecule modulation of cereblon offers vast potential for the development of new therapeutics. Cereblon-binding therapeutics carry the safety risks of thalidomide, which caused an epidemic of severe birth defects characterized by forelimb shortening or phocomelia. Here we show th...

journal_title：Nature chemical biology

authors： Matyskiela ME,Couto S,Zheng X,Lu G,Hui J,Stamp K,Drew C,Ren Y,Wang M,Carpenter A,Lee CW,Clayton T,Fang W,Lu CC,Riley M,Abdubek P,Blease K,Hartke J,Kumar G,Vessey R,Rolfe M,Hamann LG,Chamberlain PP

更新日期：2018-10-01 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：:The catalytic versatility of cytochrome P450 monooxygenases is remarkable. Here, we present mechanistic and structural characterizations of TleB from Streptomyces blastmyceticus and its homolog HinD from Streptoalloteichus hindustanus, which catalyze unusual intramolecular C-N bond formation to generate indolactam V f...

journal_title：Nature chemical biology

authors： He F,Mori T,Morita I,Nakamura H,Alblova M,Hoshino S,Awakawa T,Abe I

更新日期：2019-12-01 00:00:00

abstract：:Cholinesterase inhibitors, the current frontline symptomatic treatment for Alzheimer's disease (AD), are associated with low efficacy and adverse effects. M1 muscarinic acetylcholine receptors (M1 mAChRs) represent a potential alternate therapeutic target; however, drug discovery programs focused on this G protein-cou...

journal_title：Nature chemical biology

authors： Bradley SJ,Molloy C,Valuskova P,Dwomoh L,Scarpa M,Rossi M,Finlayson L,Svensson KA,Chernet E,Barth VN,Gherbi K,Sykes DA,Wilson CA,Mistry R,Sexton PM,Christopoulos A,Mogg AJ,Rosethorne EM,Sakata S,John Challiss RA,B

更新日期：2020-03-01 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：:Small-molecule inhibitors of kinesin-5 (refs. 1-3), a protein essential for eukaryotic cell division, represent alternatives to antimitotic agents that target tubulin. While tubulin is needed for multiple intracellular processes, the known functions of kinesin-5 are limited to dividing cells, making it likely that kin...

journal_title：Nature chemical biology

authors： Kwok BH,Kapitein LC,Kim JH,Peterman EJ,Schmidt CF,Kapoor TM

更新日期：2006-09-01 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：:Transient receptor potential (TRP) proteins form plasma-membrane cation channels that act as sensors for diverse cellular stimuli. Here, we report a novel activation mechanism mediated by cysteine S-nitrosylation in TRP channels. Recombinant TRPC1, TRPC4, TRPC5, TRPV1, TRPV3 and TRPV4 of the TRPC and TRPV families, wh...

journal_title：Nature chemical biology

authors： Yoshida T,Inoue R,Morii T,Takahashi N,Yamamoto S,Hara Y,Tominaga M,Shimizu S,Sato Y,Mori Y

更新日期：2006-11-01 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：: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：: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：:Helical membrane proteins are typically assumed to attain stable transmembrane topologies immediately upon co-translational membrane insertion. Here we show that unassembled monomers of the small multidrug resistance (SMR) family exist in a dynamic equilibrium where the N-terminal transmembrane helix flips in and out ...

journal_title：Nature chemical biology

authors： Seurig M,Ek M,von Heijne G,Fluman N

更新日期：2019-10-01 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：:AMPA receptors mediate fast excitatory neurotransmission by converting chemical signals into electrical signals, and thus it is important to understand the relationship between their chemical biology and their function. We used single-molecule fluorescence resonance energy transfer to examine the conformations explore...

journal_title：Nature chemical biology

authors： Landes CF,Rambhadran A,Taylor JN,Salatan F,Jayaraman V

更新日期：2011-03-01 00:00:00

abstract：:Clinically significant antibiotic resistance has evolved against virtually every antibiotic deployed. Yet the development of new classes of antibiotics has lagged far behind our growing need for such drugs. Rather than focusing on therapeutics that target in vitro viability, much like conventional antibiotics, an alte...

journal_title：Nature chemical biology

authors： Clatworthy AE,Pierson E,Hung DT

更新日期：2007-09-01 00:00:00

abstract：:The discovery of functional RNAs that are critical for normal and disease physiology continues to expand at a breakneck pace. Many RNA functions are controlled by the formation of specific structures, and an understanding of each structural component is necessary to elucidate its function. Measuring solvent accessibil...

journal_title：Nature chemical biology

authors： Feng C,Chan D,Joseph J,Muuronen M,Coldren WH,Dai N,Corrêa IR Jr,Furche F,Hadad CM,Spitale RC

更新日期：2018-03-01 00:00:00

abstract：:Miniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPα-Tyr, a designed peptide comprising an α-helix buttressed by a polyproline II helix. PPα-Tyr is water soluble and monomeric, and it unfolds cooperatively with a midpoint unfolding...

journal_title：Nature chemical biology

authors： Baker EG,Williams C,Hudson KL,Bartlett GJ,Heal JW,Porter Goff KL,Sessions RB,Crump MP,Woolfson DN

更新日期：2017-07-01 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：:Naphthalene (1) and para-dichlorobenzene (PDCB, 2), which are widely used as moth repellents and air fresheners, cause cancer in rodents and are potential human carcinogens. However, their mechanisms of action remain unclear. Here we describe a novel method for delivering and screening hydrophobic chemicals in C. eleg...

journal_title：Nature chemical biology

authors： Kokel D,Li Y,Qin J,Xue D

更新日期：2006-06-01 00:00:00

abstract：:Genetic screens in cultured human cells represent a powerful unbiased strategy to identify cellular pathways that determine drug efficacy, providing critical information for clinical development. We used insertional mutagenesis-based screens in haploid cells to identify genes required for the sensitivity to lasonolide...

journal_title：Nature chemical biology

authors： Dubey R,Stivala CE,Nguyen HQ,Goo YH,Paul A,Carette JE,Trost BM,Rohatgi R

更新日期：2020-02-01 00:00:00

abstract：:Beyond established roles in collagen biosynthesis, hypoxic signaling and fatty acid metabolism, recent reports have now revealed roles for human 2-oxoglutarate-dependent oxygenases in histone and nucleic acid demethylation and in signaling protein hydroxylation. The emerging role of these oxygenases in enabling a mult...

journal_title：Nature chemical biology

authors： Loenarz C,Schofield CJ

更新日期：2008-03-01 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