Identification of a S. aureus virulence factor by activity-based protein profiling (ABPP).

abstract：:Pseudouridine synthases (PUSs) are responsible for installation of pseudouridine (Ψ) modification in RNA. However, the activity and function of the PUS enzymes remain largely unexplored. Here we focus on human PUS10 and find that it co-expresses with the microprocessor (DROSHA-DGCR8 complex). Depletion of PUS10 result...

journal_title：Nature chemical biology

authors： Song J,Zhuang Y,Zhu C,Meng H,Lu B,Xie B,Peng J,Li M,Yi C

更新日期：2020-02-01 00:00:00

abstract：:More than 30 years ago, a calcium-dependent enzyme activity was described that generates N-acyl phosphatidylethanolamines (NAPEs), which are precursors for N-acyl ethanolamine (NAE) lipid transmitters, including the endocannabinoid anandamide. The identity of this calcium-dependent N-acyltransferase (Ca-NAT) has remai...

journal_title：Nature chemical biology

authors： Ogura Y,Parsons WH,Kamat SS,Cravatt BF

更新日期：2016-09-01 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：:Identifying targets of antibacterial compounds remains a challenging step in the development of antibiotics. We have developed a two-pronged functional genomics approach to predict mechanism of action that uses mutant fitness data from antibiotic-treated transposon libraries containing both upregulation and inactivati...

journal_title：Nature chemical biology

authors： Santiago M,Lee W,Fayad AA,Coe KA,Rajagopal M,Do T,Hennessen F,Srisuknimit V,Müller R,Meredith TC,Walker S

更新日期：2018-06-01 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 cellular proteins require iron cofactors for activity, and cells express systems for their assembly and distribution. Molecular details of the cytosolic iron pool used for iron cofactors are lacking, but iron chaperones of the poly(rC)-binding protein (PCBP) family play a key role in ferrous ion distributi...

journal_title：Nature chemical biology

authors： Patel SJ,Frey AG,Palenchar DJ,Achar S,Bullough KZ,Vashisht A,Wohlschlegel JA,Philpott CC

更新日期：2019-09-01 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：: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：: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：:Nitrite represents a bioactive reservoir of nitric oxide (NO) that may modulate vasodilation, respiration and cytoprotection after ischemia-reperfusion injury. Although nitrite formation is thought to occur via reaction of NO with oxygen, this third-order reaction cannot compete kinetically with the reaction of NO wit...

journal_title：Nature chemical biology

authors： Shiva S,Wang X,Ringwood LA,Xu X,Yuditskaya S,Annavajjhala V,Miyajima H,Hogg N,Harris ZL,Gladwin MT

更新日期：2006-09-01 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：:Ferroptosis is a form of regulated necrotic cell death controlled by glutathione peroxidase 4 (GPX4). At present, mechanisms that could predict sensitivity and/or resistance and that may be exploited to modulate ferroptosis are needed. We applied two independent approaches-a genome-wide CRISPR-based genetic screen and...

journal_title：Nature chemical biology

authors： Doll S,Proneth B,Tyurina YY,Panzilius E,Kobayashi S,Ingold I,Irmler M,Beckers J,Aichler M,Walch A,Prokisch H,Trümbach D,Mao G,Qu F,Bayir H,Füllekrug J,Scheel CH,Wurst W,Schick JA,Kagan VE,Angeli JP,Conrad M

更新日期：2017-01-01 00:00:00

abstract：:Cell polarity is the asymmetric compartmentalization of cellular components. An opposing gradient of partitioning-defective protein kinases, atypical protein kinase C (aPKC) and PAR-1, at the cell cortex guides diverse asymmetries in the structure of metazoan cells, but the mechanism underlying their spatial patternin...

journal_title：Nature chemical biology

authors： Ramanujam R,Han Z,Zhang Z,Kanchanawong P,Motegi F

更新日期：2018-10-01 00:00:00

abstract：:Small ubiquitin-like modifier (SUMO) family proteins regulate target-protein functions by post-translational modification. However, a potent and selective inhibitor targeting the SUMO pathway has been lacking. Here we describe ML-792, a mechanism-based SUMO-activating enzyme (SAE) inhibitor with nanomolar potency in c...

journal_title：Nature chemical biology

authors： He X,Riceberg J,Soucy T,Koenig E,Minissale J,Gallery M,Bernard H,Yang X,Liao H,Rabino C,Shah P,Xega K,Yan ZH,Sintchak M,Bradley J,Xu H,Duffey M,England D,Mizutani H,Hu Z,Guo J,Chau R,Dick LR,Brownell JE,Ne

更新日期：2017-11-01 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：:Mucopolysaccharidosis type I (MPS I), caused by mutations in the gene encoding α-L-iduronidase (IDUA), is one of approximately 70 genetic disorders collectively known as the lysosomal storage diseases. To gain insight into the basis for MPS I, we crystallized human IDUA produced in an Arabidopsis thaliana cgl mutant. ...

journal_title：Nature chemical biology

authors： Bie H,Yin J,He X,Kermode AR,Goddard-Borger ED,Withers SG,James MN

更新日期：2013-11-01 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：:The structure-specific nuclease human flap endonuclease-1 (hFEN1) plays a key role in DNA replication and repair and may be of interest as an oncology target. We present the crystal structure of inhibitor-bound hFEN1, which shows a cyclic N-hydroxyurea bound in the active site coordinated to two magnesium ions. Three ...

journal_title：Nature chemical biology

authors： Exell JC,Thompson MJ,Finger LD,Shaw SJ,Debreczeni J,Ward TA,McWhirter C,Siöberg CL,Martinez Molina D,Abbott WM,Jones CD,Nissink JW,Durant ST,Grasby JA

更新日期：2016-10-01 00:00:00

abstract：:Oxidase and oxygenase enzymes allow the use of relatively unreactive O2 in biochemical reactions. Many of the mechanistic strategies used in nature for this key reaction are represented within the 2-histidine-1-carboxylate facial triad family of non-heme Fe(II)-containing enzymes. The open face of the metal coordinati...

journal_title：Nature chemical biology

authors： Kovaleva EG,Lipscomb JD

更新日期：2008-03-01 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：: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 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：: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：: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：: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：:Sulfoquinovose is produced by photosynthetic organisms at a rate of 10(10) tons per annum and is degraded by bacteria as a source of carbon and sulfur. We have identified Escherichia coli YihQ as the first dedicated sulfoquinovosidase and the gateway enzyme to sulfoglycolytic pathways. Structural and mutagenesis studi...

journal_title：Nature chemical biology

authors： Speciale G,Jin Y,Davies GJ,Williams SJ,Goddard-Borger ED

更新日期：2016-04-01 00:00:00

abstract：:Enzymatic incorporation of a halogen atom is a common feature in the biosyntheses of more than 4,500 natural products. Halogenation of unactivated carbon centers in the biosyntheses of several compounds of nonribosomal peptide origin is carried out by a class of mononuclear nonheme iron enzymes that require alpha-keto...

journal_title：Nature chemical biology

authors： Galonić DP,Barr EW,Walsh CT,Bollinger JM Jr,Krebs C

更新日期：2007-02-01 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：: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：: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