Making carbon-nitrogen bonds in biological and chemical synthesis.

abstract：:Bifunctional Rel stringent factors, the most abundant class of RelA/SpoT homologs, are ribosome-associated enzymes that transfer a pyrophosphate from ATP onto the 3' of guanosine tri-/diphosphate (GTP/GDP) to synthesize the bacterial alarmone (p)ppGpp, and also catalyze the 3' pyrophosphate hydrolysis to degrade it. T...

journal_title：Nature chemical biology

authors： Tamman H,Van Nerom K,Takada H,Vandenberk N,Scholl D,Polikanov Y,Hofkens J,Talavera A,Hauryliuk V,Hendrix J,Garcia-Pino A

更新日期：2020-08-01 00:00:00

abstract：:DNA polymerases catalyze efficient and high-fidelity DNA synthesis. While this reaction favors nucleotide incorporation, polymerases also catalyze a reverse reaction, pyrophosphorolysis, that removes the DNA primer terminus and generates deoxynucleoside triphosphates. Because pyrophosphorolysis can influence polymeras...

journal_title：Nature chemical biology

authors： Shock DD,Freudenthal BD,Beard WA,Wilson SH

更新日期：2017-10-01 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：:A 2.4-Å-resolution X-ray crystal structure of the carrier-protein-independent halogenase WelO5 in complex with its welwitindolinone precursor substrate, 12-epi-fischerindole U, reveals that the C13 chlorination target is proximal to the anticipated site of the oxo group in a presumptive cis-halo-oxo-iron(IV) (haloferr...

journal_title：Nature chemical biology

authors： Mitchell AJ,Zhu Q,Maggiolo AO,Ananth NR,Hillwig ML,Liu X,Boal AK

更新日期：2016-08-01 00:00:00

abstract：:N(1)-Methyladenosine (m(1)A) is a prevalent post-transcriptional RNA modification, yet little is known about its abundance, topology and dynamics in mRNA. Here, we show that m(1)A is prevalent in Homo sapiens mRNA, which shows an m(1)A/A ratio of ∼0.02%. We develop the m(1)A-ID-seq technique, based on m(1)A immunoprec...

journal_title：Nature chemical biology

authors： Li X,Xiong X,Wang K,Wang L,Shu X,Ma S,Yi C

更新日期：2016-05-01 00:00:00

abstract：:The inability of cells to properly fold, modify and assemble secretory and transmembrane proteins leads to accumulation of misfolded proteins in the endoplasmic reticulum (ER). Under these conditions of 'ER stress', cell survival depends on homeostatic benefits from an intracellular signaling pathway called the unfold...

journal_title：Nature chemical biology

authors： Maly DJ,Papa FR

更新日期：2014-11-01 00:00:00

abstract：:Serine hydrolases play diverse roles in regulating host-pathogen interactions in a number of organisms, yet few have been characterized in the human pathogen Staphylococcus aureus. Here we describe a chemical proteomic screen that identified ten previously uncharacterized S. aureus serine hydrolases that mostly lack h...

journal_title：Nature chemical biology

authors： Lentz CS,Sheldon JR,Crawford LA,Cooper R,Garland M,Amieva MR,Weerapana E,Skaar EP,Bogyo M

更新日期：2018-06-01 00:00:00

abstract：:Chemistry drives many biological interactions between the microbiota and host animals, yet it is often challenging to identify the chemicals involved. This poses a problem, as such small molecules are excellent sources of potential pharmaceuticals, pretested by nature for animal compatibility. We discovered anti-HIV c...

journal_title：Nature chemical biology

authors： Smith TE,Pond CD,Pierce E,Harmer ZP,Kwan J,Zachariah MM,Harper MK,Wyche TP,Matainaho TK,Bugni TS,Barrows LR,Ireland CM,Schmidt EW

更新日期：2018-02-01 00:00:00

abstract：:Small molecules that specifically activate an intracellular protein of interest are highly desirable. A generally applicable strategy, however, remains elusive. Herein we describe a small molecule-triggered bioorthogonal protein decaging technique that relies on the inverse electron-demand Diels-Alder reaction for eli...

journal_title：Nature chemical biology

authors： Li J,Jia S,Chen PR

更新日期：2014-12-01 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：:Bacterial biofilms can be programmed to produce living materials with self-healing and evolvable functionalities. However, the wider use of artificial biofilms has been hindered by limitations on processability and functional protein secretion capacity. We describe a highly flexible and tunable living functional mater...

journal_title：Nature chemical biology

authors： Huang J,Liu S,Zhang C,Wang X,Pu J,Ba F,Xue S,Ye H,Zhao T,Li K,Wang Y,Zhang J,Wang L,Fan C,Lu TK,Zhong C

更新日期：2019-01-01 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：:Mutation and aberrant expression of apoptotic proteins are hallmarks of cancer. These changes prevent proapoptotic signals from being transmitted to executioner caspases, thereby averting apoptotic death and allowing cellular proliferation. Caspase-3 is the key executioner caspase, and it exists as an inactive zymogen...

journal_title：Nature chemical biology

authors： Putt KS,Chen GW,Pearson JM,Sandhorst JS,Hoagland MS,Kwon JT,Hwang SK,Jin H,Churchwell MI,Cho MH,Doerge DR,Helferich WG,Hergenrother PJ

更新日期：2006-10-01 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：: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：: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：: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：:RNA G-quadruplex (G4) structures are thought to affect biological processes, including translation and pre-mRNA splicing, but it is not possible at present to demonstrate that they form naturally at specific sequences in long functional RNA molecules. We developed a new strategy, footprinting of long 7-deazaguanine-su...

journal_title：Nature chemical biology

authors： Weldon C,Behm-Ansmant I,Hurley LH,Burley GA,Branlant C,Eperon IC,Dominguez C

更新日期：2017-01-01 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：:Cell-permeable small molecules that inhibit their targets on fast timescales are powerful probes of cell-division mechanisms. Such inhibitors have been identified using phenotype-based screens with chemical libraries. However, the characteristics of compound libraries needed to effectively span cell-division phenotype...

journal_title：Nature chemical biology

authors： Peters U,Cherian J,Kim JH,Kwok BH,Kapoor TM

更新日期：2006-11-01 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：: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：: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：:The phytohormone auxin indole-3-acetic acid (IAA) regulates nearly all aspects of plant growth and development. Despite substantial progress in our understanding of auxin biology, delineating specific auxin response remains a major challenge. Auxin regulates transcriptional response via its receptors, TIR1 and AFB F-b...

journal_title：Nature chemical biology

authors： Uchida N,Takahashi K,Iwasaki R,Yamada R,Yoshimura M,Endo TA,Kimura S,Zhang H,Nomoto M,Tada Y,Kinoshita T,Itami K,Hagihara S,Torii KU

更新日期：2018-03-01 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：: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：: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

abstract：:Inorganic nitrite (NO(2)(-)) is emerging as a regulator of physiological functions and tissue responses to ischemia, whereas the more stable nitrate anion (NO(3)(-)) is generally considered to be biologically inert. Bacteria express nitrate reductases that produce nitrite, but mammals lack these specific enzymes. Here...

journal_title：Nature chemical biology

authors： Jansson EA,Huang L,Malkey R,Govoni M,Nihlén C,Olsson A,Stensdotter M,Petersson J,Holm L,Weitzberg E,Lundberg JO

更新日期：2008-07-01 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：: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