ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition.

abstract：:Although the protein synthesis inhibitor cycloheximide (CHX) has been known for decades, its precise mechanism of action remains incompletely understood. The glutarimide portion of CHX is seen in a family of structurally related natural products including migrastatin, isomigrastatin and lactimidomycin (LTM). We found ...

journal_title：Nature chemical biology

authors： Schneider-Poetsch T,Ju J,Eyler DE,Dang Y,Bhat S,Merrick WC,Green R,Shen B,Liu JO

更新日期：2010-03-01 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

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：:Thiazole/oxazole-modified microcins (TOMMs) encompass a recently defined class of ribosomally synthesized natural products with a diverse set of biological activities. Although TOMM biosynthesis has been investigated for over a decade, the mechanism of heterocycle formation by the synthetase enzymes remains poorly und...

journal_title：Nature chemical biology

authors： Dunbar KL,Melby JO,Mitchell DA

更新日期：2012-04-22 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：:Lysine riboswitches are bacterial RNA structures that sense the concentration of lysine and regulate the expression of lysine biosynthesis and transport genes. Members of this riboswitch class are found in the 5' untranslated region of messenger RNAs, where they form highly selective receptors for lysine. Lysine bindi...

journal_title：Nature chemical biology

authors： Blount KF,Wang JX,Lim J,Sudarsan N,Breaker RR

更新日期：2007-01-01 00:00:00

abstract：:Single-molecule observations reveal that lipid- and protein-based interactions jointly contribute to the interactions among glycosylphosphatidylinositol-anchored proteins in membranes. Understanding these interactions will help to refine long-evolving (and still debated) models of 'raft' domains in biological membrane...

journal_title：Nature chemical biology

authors： Silvius JR

更新日期：2012-09-01 00:00:00

abstract：:Conditional cooperativity is a common mechanism involved in transcriptional regulation of prokaryotic type II toxin-antitoxin operons and is intricately related to bacterial persistence. It allows the toxin component of a toxin-antitoxin module to act as a co-repressor at low doses of toxin as compared to antitoxin. W...

journal_title：Nature chemical biology

authors： Garcia-Pino A,De Gieter S,Talavera A,De Greve H,Efremov RG,Loris R

更新日期：2016-07-01 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：:Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vi...

journal_title：Nature chemical biology

authors： Ferguson FM,Nabet B,Raghavan S,Liu Y,Leggett AL,Kuljanin M,Kalekar RL,Yang A,He S,Wang J,Ng RWS,Sulahian R,Li L,Poulin EJ,Huang L,Koren J,Dieguez-Martinez N,Espinosa S,Zeng Z,Corona CR,Vasta JD,Ohi R,Sim T,K

更新日期：2020-06-01 00:00:00

abstract：:MicroRNAs are evolutionarily conserved small, noncoding RNAs that regulate diverse biological processes. Due to their essential regulatory roles, microRNA biogenesis is tightly regulated, where protein factors are often found to interact with specific primary and precursor microRNAs for regulation. Here, using NMR rel...

journal_title：Nature chemical biology

authors： Baisden JT,Boyer JA,Zhao B,Hammond SM,Zhang Q

更新日期：2021-01-01 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：:Foldamers are sequence-specific oligomers akin to peptides, proteins and oligonucleotides that fold into well-defined three-dimensional structures. They offer the chemical biologist a broad pallet of building blocks for the construction of molecules that test and extend our understanding of protein folding and functio...

journal_title：Nature chemical biology

authors： Goodman CM,Choi S,Shandler S,DeGrado WF

更新日期：2007-05-01 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：: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

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：: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：: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：:The lasso peptide microcin J25 is known to hijack the siderophore receptor FhuA for initiating internalization. Here, we provide what is to our knowledge the first structural evidence on the recognition mechanism, and our biochemical data show that another closely related lasso peptide cannot interact with FhuA. Our w...

journal_title：Nature chemical biology

authors： Mathavan I,Zirah S,Mehmood S,Choudhury HG,Goulard C,Li Y,Robinson CV,Rebuffat S,Beis K

更新日期：2014-05-01 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：:Lipid rafts in plasma membranes have emerged as possible platforms for the entry of HIV and other viruses into cells. However, little is known about how lipid phase heterogeneity contributes to viral entry because of the fine-grained and still poorly understood complexity of biological membranes. We used model systems...

journal_title：Nature chemical biology

authors： Yang ST,Kiessling V,Simmons JA,White JM,Tamm LK

更新日期：2015-06-01 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：:Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity ...

journal_title：Nature chemical biology

authors： Rees MG,Seashore-Ludlow B,Cheah JH,Adams DJ,Price EV,Gill S,Javaid S,Coletti ME,Jones VL,Bodycombe NE,Soule CK,Alexander B,Li A,Montgomery P,Kotz JD,Hon CS,Munoz B,Liefeld T,Dančík V,Haber DA,Clish CB,Bittker JA

更新日期：2016-02-01 00:00:00

abstract：:Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, ...

journal_title：Nature chemical biology

authors： Rzuczek SG,Colgan LA,Nakai Y,Cameron MD,Furling D,Yasuda R,Disney MD

更新日期：2017-02-01 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：: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：: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 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：:The chemical species involved in H2S signaling remain elusive despite the profound and pleiotropic physiological effects elicited by this molecule. The dominant candidate mechanism for sulfide signaling is persulfidation of target proteins. However, the relatively poor reactivity of H2S toward oxidized thiols, such as...

journal_title：Nature chemical biology

authors： Mishanina TV,Libiad M,Banerjee R

更新日期：2015-07-01 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