Mammalian circadian signaling networks and therapeutic targets.

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：: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：: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：:CRISPR-Cas9 has emerged as a powerful technology that enables ready modification of the mammalian genome. The ability to modulate Cas9 activity can reduce off-target cleavage and facilitate precise genome engineering. Here we report the development of a Cas9 variant whose activity can be switched on and off in human c...

journal_title：Nature chemical biology

authors： Liu KI,Ramli MN,Woo CW,Wang Y,Zhao T,Zhang X,Yim GR,Chong BY,Gowher A,Chua MZ,Jung J,Lee JH,Tan MH

更新日期：2016-11-01 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：: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：: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：:Biodiversity, or the relative abundance of species, measures the persistence of an ecosystem. To better understand its modulation, we analyzed the spatial and temporal dynamics of a synthetic, chemical-mediated ecosystem that consisted of two engineered Escherichia coli populations. Depending on the specific experimen...

journal_title：Nature chemical biology

authors： Song H,Payne S,Gray M,You L

更新日期：2009-12-01 00:00:00

abstract：:Thiolutin is a disulfide-containing antibiotic and anti-angiogenic compound produced by Streptomyces. Its biological targets are not known. We show that reduced thiolutin is a zinc chelator that inhibits the JAB1/MPN/Mov34 (JAMM) domain-containing metalloprotease Rpn11, a deubiquitinating enzyme of the 19S proteasome....

journal_title：Nature chemical biology

authors： Lauinger L,Li J,Shostak A,Cemel IA,Ha N,Zhang Y,Merkl PE,Obermeyer S,Stankovic-Valentin N,Schafmeier T,Wever WJ,Bowers AA,Carter KP,Palmer AE,Tschochner H,Melchior F,Deshaies RJ,Brunner M,Diernfellner A

更新日期：2017-07-01 00:00:00

abstract：:In this study, we demonstrate the feasibility of expanding the genetic code of Escherichia coli using its own tryptophanyl-tRNA synthetase and tRNA (TrpRS-tRNATrp) pair. This was made possible by first functionally replacing this endogenous pair with an E. coli-optimized counterpart from Saccharomyces cerevisiae, and ...

journal_title：Nature chemical biology

authors： Italia JS,Addy PS,Wrobel CJ,Crawford LA,Lajoie MJ,Zheng Y,Chatterjee A

更新日期：2017-04-01 00:00:00

abstract：: ...

journal_title：Nature chemical biology

authors： Deane C

更新日期：2018-06-01 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：: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：:Changes in the cellular environment modulate protein energy landscapes to drive important biology, with consequences for signaling, allostery and other vital processes. The effects of ubiquitination are particularly important because of their potential influence on degradation by the 26S proteasome. Moreover, proteaso...

journal_title：Nature chemical biology

authors： Carroll EC,Greene ER,Martin A,Marqusee S

更新日期：2020-08-01 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：:Using linewidth and spinning sideband intensities of lipid hydrocarbon chain resonances in proton magic angle spinning NMR spectra, we detected the temperature-dependent phase state of naturally occurring lipids of intact influenza virus without exogenous probes. Increasingly, below 41 degrees C ordered and disordered...

journal_title：Nature chemical biology

authors： Polozov IV,Bezrukov L,Gawrisch K,Zimmerberg J

更新日期：2008-04-01 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：: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：:Twister is a small ribozyme present in almost all kingdoms of life that rapidly self-cleaves in variety of divalent metal ions. We used activity assays, bulk FRET and single-molecule FRET (smFRET) to understand how different metal ions promote folding and self-cleavage of the Oryza sativa twister ribozyme. Although mo...

journal_title：Nature chemical biology

authors： Panja S,Hua B,Zegarra D,Ha T,Woodson SA

更新日期：2017-10-01 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：: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：:The nematode Caenorhabditis elegans requires exogenous cholesterol to survive and its depletion leads to early developmental arrest. Thus, tight regulation of cholesterol storage and distribution within the organism is indispensable. Here, we present a novel class of C. elegans phosphorylated glycosphingolipids, phosp...

journal_title：Nature chemical biology

authors： Boland S,Schmidt U,Zagoriy V,Sampaio JL,Fritsche RF,Czerwonka R,Lübken T,Reimann J,Penkov S,Knölker HJ,Kurzchalia TV

更新日期：2017-06-01 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：: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：: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：: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：:Nature is a diverse and rich source of bioactive pathways or novel building blocks for synthetic biology. In this Perspective, we describe the emerging research field in which metagenomes are functionally interrogated using synthetic biology. This approach substantially expands the set of identified biological activit...

journal_title：Nature chemical biology

authors： van der Helm E,Genee HJ,Sommer MOA

更新日期：2018-08-01 00:00:00

abstract：:Actin filament dynamics are critical in cell motility. The structure of actin filament changes spontaneously and can also be regulated by actin-binding proteins, allowing actin to readily function in response to external stimuli. The interaction with the motor protein myosin changes the dynamic nature of actin filamen...

journal_title：Nature chemical biology

authors： Kozuka J,Yokota H,Arai Y,Ishii Y,Yanagida T

更新日期：2006-02-01 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：: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