Cleavage of a carbon-fluorine bond by an engineered cysteine dioxygenase.

abstract：:Regulation of gene expression in response to the changing environment is critical for cell survival. For instance, binding of macrolide antibiotics to the ribosome promotes translation arrest at the leader open reading frames ermCL and ermBL, which is necessary for inducing the antibiotic resistance genes ermC and erm...

journal_title：Nature chemical biology

authors： Gupta P,Liu B,Klepacki D,Gupta V,Schulten K,Mankin AS,Vázquez-Laslop N

更新日期：2016-03-01 00:00:00

abstract：:Molecular dynamics are essential for protein function. In some cases these dynamics involve the interconversion between ground state, highly populated conformers and less populated higher energy structures ('excited states') that play critical roles in biochemical processes. Here we describe recent advances in NMR spe...

journal_title：Nature chemical biology

authors： Baldwin AJ,Kay LE

更新日期：2009-11-01 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：: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 rise of antibiotic resistance demands the acceleration of molecular diversification strategies to inspire new chemical entities for antibiotic medicines. We report here on the large-scale engineering of ribosomally synthesized and post-translationally modified antimicrobial peptides carrying the ring-forming amino...

journal_title：Nature chemical biology

authors： Schmitt S,Montalbán-López M,Peterhoff D,Deng J,Wagner R,Held M,Kuipers OP,Panke S

更新日期：2019-05-01 00:00:00

abstract：:Biosynthesis enables renewable production of manifold compounds, yet often biosynthetic performance must be improved for it to be economically feasible. Nongenetic, cell-to-cell variations in protein and metabolite concentrations are naturally inherent, suggesting the existence of both high- and low-performance varian...

journal_title：Nature chemical biology

authors： Xiao Y,Bowen CH,Liu D,Zhang F

更新日期：2016-05-01 00:00:00

abstract：:The ykkC family of bacterial riboswitches combines several widespread classes that have similar secondary structures and consensus motifs but control different genes in response to different cellular metabolites. Here we report the crystal structures of two distinct ykkC riboswitches specifically bound to their cognat...

journal_title：Nature chemical biology

authors： Peselis A,Serganov A

更新日期：2018-09-01 00:00:00

abstract：:Antibody-drug conjugates (ADCs) selectively deliver chemotherapeutic agents to target cells and are important cancer therapeutics. However, the mechanisms by which ADCs are internalized and activated remain unclear. Using CRISPR-Cas9 screens, we uncover many known and novel endolysosomal regulators as modulators of AD...

journal_title：Nature chemical biology

authors： Tsui CK,Barfield RM,Fischer CR,Morgens DW,Li A,Smith BAH,Gray MA,Bertozzi CR,Rabuka D,Bassik MC

更新日期：2019-10-01 00:00:00

abstract：:Protein kinase signaling along the kinetochore-centromere axis is crucial to assure mitotic fidelity, yet the details of its spatial coordination are obscure. Here, we examined how pools of human Polo-like kinase 1 (Plk1) within this axis control signaling events to elicit mitotic functions. To do this, we restricted ...

journal_title：Nature chemical biology

authors： Lera RF,Potts GK,Suzuki A,Johnson JM,Salmon ED,Coon JJ,Burkard ME

更新日期：2016-06-01 00:00:00

abstract：:Hapalindole alkaloids are a structurally diverse class of cyanobacterial natural products defined by their varied polycyclic ring systems and diverse biological activities. These complex metabolites are generated from a common biosynthetic intermediate by the Stig cyclases in three mechanistic steps: a rare Cope rearr...

journal_title：Nature chemical biology

authors： Newmister SA,Li S,Garcia-Borràs M,Sanders JN,Yang S,Lowell AN,Yu F,Smith JL,Williams RM,Houk KN,Sherman DH

更新日期：2018-04-01 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：: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：: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：:Biotin is an essential vitamin in plants and mammals, functioning as the carbon dioxide carrier within central lipid metabolism. Bacterial pimeloyl-CoA synthetase (BioW) acts as a highly specific substrate-selection gate, ensuring the integrity of the carbon chain in biotin synthesis. BioW catalyzes the condensation o...

journal_title：Nature chemical biology

authors： Wang M,Moynié L,Harrison PJ,Kelly V,Piper A,Naismith JH,Campopiano DJ

更新日期：2017-06-01 00:00:00

abstract：:Benzylisoquinoline alkaloids (BIAs) are a diverse family of plant-specialized metabolites that include the pharmaceuticals codeine and morphine and their derivatives. Microbial synthesis of BIAs holds promise as an alternative to traditional crop-based manufacturing. Here we demonstrate the production of the key BIA i...

journal_title：Nature chemical biology

authors： DeLoache WC,Russ ZN,Narcross L,Gonzales AM,Martin VJ,Dueber JE

更新日期：2015-07-01 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：:To maximize a desired product, metabolic engineers typically express enzymes to high, constant levels. Yet, permanent pathway activation can have undesirable consequences including competition with essential pathways and accumulation of toxic intermediates. Faced with similar challenges, natural metabolic systems comp...

journal_title：Nature chemical biology

authors： Zhao EM,Suek N,Wilson MZ,Dine E,Pannucci NL,Gitai Z,Avalos JL,Toettcher JE

更新日期：2019-06-01 00:00:00

abstract：:What do organic synthesis, mechanistic enzymology, structural biology and glycoscience have in common? They all span chemistry and biology, benefit from and contribute to multidisciplinary approaches, and were up for discussion at a recent symposium in Dublin. ...

journal_title：Nature chemical biology

authors： Murphy PV,Rutledge PJ

更新日期：2006-02-01 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：:Trafficking and sorting of membrane-anchored Ras GTPases are regulated by partitioning between distinct membrane domains. Here, in vitro experiments and microscopic molecular theory reveal membrane curvature as a new modulator of N-Ras lipid anchor and palmitoyl chain partitioning. Membrane curvature was essential for...

journal_title：Nature chemical biology

authors： Larsen JB,Jensen MB,Bhatia VK,Pedersen SL,Bjørnholm T,Iversen L,Uline M,Szleifer I,Jensen KJ,Hatzakis NS,Stamou D

更新日期：2015-03-01 00:00:00

abstract：:We engineered a photoactivatable system for rapidly and reversibly exporting proteins from the nucleus by embedding a nuclear export signal in the LOV2 domain from phototropin 1. Fusing the chromatin modifier Bre1 to the photoswitch, we achieved light-dependent control of histone H2B monoubiquitylation in yeast, revea...

journal_title：Nature chemical biology

authors： Yumerefendi H,Lerner AM,Zimmerman SP,Hahn K,Bear JE,Strahl BD,Kuhlman B

更新日期：2016-06-01 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：: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：: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：: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：:The function of many biologically active molecules requires the presence of carbon-nitrogen bonds in strategic positions. The biosynthetic pathways leading to such bonds can be bypassed through chemical synthesis to synthesize natural products more efficiently and also to generate the molecular diversity unavailable i...

journal_title：Nature chemical biology

authors： Hili R,Yudin AK

更新日期：2006-06-01 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：:The GATOR1 (SEACIT) complex consisting of Iml1-Npr2-Npr3 inhibits target of rapamycin complex 1 (TORC1) in response to amino acid insufficiency. In glucose medium, Saccharomyces cerevisiae mutants lacking the function of this complex grow poorly in the absence of amino acid supplementation, despite showing hallmarks o...

journal_title：Nature chemical biology

authors： Chen J,Sutter BM,Shi L,Tu BP

更新日期：2017-11-01 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：: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