Serine is a new target residue for endogenous ADP-ribosylation on histones.

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：:Phosphorylation and glycosylation of the tau protein, which is implicated in neurodegenerative diseases, are intimately linked. In vivo pharmacological inhibition of tau deglycosylation may be a new way to suppress abnormal tau phosphorylation, known to be involved in the formation of neurofibrillary tangles in the br...

journal_title：Nature chemical biology

authors： Fischer PM

更新日期：2008-08-01 00:00:00

abstract：:The MerR-family transcription factors (TFs) are a large group of bacterial proteins responding to cellular metal ions and multiple antibiotics by binding within central RNA polymerase-binding regions of a promoter. While most TFs alter transcription through protein-protein interactions, MerR TFs are capable of reshapi...

journal_title：Nature chemical biology

authors： Fang C,Philips SJ,Wu X,Chen K,Shi J,Shen L,Xu J,Feng Y,O'Halloran TV,Zhang Y

更新日期：2021-01-01 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：: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：:The With-No-Lysine (K) (WNK) kinases play a critical role in blood pressure regulation and body fluid and electrolyte homeostasis. Herein, we introduce the first orally bioavailable pan-WNK-kinase inhibitor, WNK463, that exploits unique structural features of the WNK kinases for both affinity and kinase selectivity. I...

journal_title：Nature chemical biology

authors： Yamada K,Park HM,Rigel DF,DiPetrillo K,Whalen EJ,Anisowicz A,Beil M,Berstler J,Brocklehurst CE,Burdick DA,Caplan SL,Capparelli MP,Chen G,Chen W,Dale B,Deng L,Fu F,Hamamatsu N,Harasaki K,Herr T,Hoffmann P,Hu QY,

更新日期：2016-11-01 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：:Controlled distribution of lipids across various cell membranes is crucial for cell homeostasis and regulation. We developed an imaging method that allows simultaneous in situ quantification of cholesterol in two leaflets of the plasma membrane (PM) using tunable orthogonal cholesterol sensors. Our imaging revealed ma...

journal_title：Nature chemical biology

authors： Liu SL,Sheng R,Jung JH,Wang L,Stec E,O'Connor MJ,Song S,Bikkavilli RK,Winn RA,Lee D,Baek K,Ueda K,Levitan I,Kim KP,Cho W

更新日期：2017-03-01 00:00:00

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：: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：:Enzyme-catalyzed peptide ligation is a powerful tool for site-specific protein bioconjugation, but stringent enzyme-substrate specificity limits its utility. We developed an approach for comprehensively characterizing peptide ligase specificity for N termini using proteome-derived peptide libraries. We used this strat...

journal_title：Nature chemical biology

authors： Weeks AM,Wells JA

更新日期：2018-01-01 00:00:00

abstract：:Identifying the interaction partners of noncoding RNAs is essential for elucidating their functions. We have developed an approach, termed microRNA crosslinking and immunoprecipitation (miR-CLIP), using pre-miRNAs modified with psoralen and biotin to capture their targets in cells. Photo-crosslinking and Argonaute 2 i...

journal_title：Nature chemical biology

authors： Imig J,Brunschweiger A,Brümmer A,Guennewig B,Mittal N,Kishore S,Tsikrika P,Gerber AP,Zavolan M,Hall J

更新日期：2015-02-01 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：: ...

journal_title：Nature chemical biology

authors： Song Y

更新日期：2019-01-01 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：:Bile salt hydrolase (BSH) enzymes are widely expressed by human gut bacteria and catalyze the gateway reaction leading to secondary bile acid formation. Bile acids regulate key metabolic and immune processes by binding to host receptors. There is an unmet need for a potent tool to inhibit BSHs across all gut bacteria ...

journal_title：Nature chemical biology

authors： Adhikari AA,Seegar TCM,Ficarro SB,McCurry MD,Ramachandran D,Yao L,Chaudhari SN,Ndousse-Fetter S,Banks AS,Marto JA,Blacklow SC,Devlin AS

更新日期：2020-03-01 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：: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：: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 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：: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：:Cysteine dioxygenase (CDO) plays an essential role in sulfur metabolism by regulating homeostatic levels of cysteine. Human CDO contains a post-translationally generated Cys93-Tyr157 cross-linked cofactor. Here, we investigated this Cys-Tyr cross-linking by incorporating unnatural tyrosines in place of Tyr157 via a ge...

journal_title：Nature chemical biology

authors： Li J,Griffith WP,Davis I,Shin I,Wang J,Li F,Wang Y,Wherritt DJ,Liu A

更新日期：2018-09-01 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：: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：: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：:Lysostaphin is a bacteriolytic enzyme targeting peptidoglycan, the essential component of the bacterial cell envelope. It displays a very potent and specific activity toward staphylococci, including methicillin-resistant Staphylococcus aureus. Lysostaphin causes rapid cell lysis and disrupts biofilms, and is therefore...

journal_title：Nature chemical biology

authors： Gonzalez-Delgado LS,Walters-Morgan H,Salamaga B,Robertson AJ,Hounslow AM,Jagielska E,Sabała I,Williamson MP,Lovering AL,Mesnage S

更新日期：2020-01-01 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：: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：:Hundreds of human proteins are modified by reversible palmitoylation of cysteine residues (S-palmitoylation), but the regulation of depalmitoylation is poorly understood. Here, we develop 'depalmitoylation probes' (DPPs), small-molecule fluorophores, to monitor the endogenous activity levels of 'erasers' of S-palmitoy...

journal_title：Nature chemical biology

authors： Kathayat RS,Elvira PD,Dickinson BC

更新日期：2017-02-01 00:00:00

abstract：:The simultaneous observation of interdependent reactions within different phases as catalyzed by membrane-bound enzymes is still a challenging task. One such enzyme, the Escherichia coli integral membrane protein diacylglycerol kinase (DGK), is a key player in lipid regulation. It catalyzes the generation of phosphati...

journal_title：Nature chemical biology

authors： Ullrich SJ,Hellmich UA,Ullrich S,Glaubitz C

更新日期：2011-05-01 00:00:00