A calcium-dependent acyltransferase that produces N-acyl phosphatidylethanolamines.

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 remained mysterious. Here, we use activity-based protein profiling to identify the poorly characterized serine hydrolase PLA2G4E as a mouse brain Ca-NAT and show that this enzyme generates NAPEs and NAEs in mammalian cells.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Ogura Y,Parsons WH,Kamat SS,Cravatt BF

doi

10.1038/nchembio.2127

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

669-71

issue

9

eissn

1552-4450

issn

1552-4469

pii

nchembio.2127

journal_volume

12

pub_type

杂志文章
  • SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate.

    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

    pub_type: 杂志文章

    doi:10.1038/s41589-018-0129-x

    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

  • A cell wall recycling shortcut that bypasses peptidoglycan de novo biosynthesis.

    abstract::We report a salvage pathway in Gram-negative bacteria that bypasses de novo biosynthesis of UDP N-acetylmuramic acid (UDP-MurNAc), the first committed peptidoglycan precursor, and thus provides a rationale for intrinsic fosfomycin resistance. The anomeric sugar kinase AmgK and the MurNAc α-1-phosphate uridylyl transfe...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1289

    authors: Gisin J,Schneider A,Nägele B,Borisova M,Mayer C

    更新日期:2013-08-01 00:00:00

  • Visualizing a protonated RNA state that modulates microRNA-21 maturation.

    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

    pub_type: 杂志文章

    doi:10.1038/s41589-020-00667-5

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

    更新日期:2021-01-01 00:00:00

  • Signaling diversity of PKA achieved via a Ca2+-cAMP-PKA oscillatory circuit.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio.478

    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

  • Correlating chemical sensitivity and basal gene expression reveals mechanism of action.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio.1986

    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

  • A propofol binding site on mammalian GABAA receptors identified by photolabeling.

    abstract::Propofol is the most important intravenous general anesthetic in current clinical use. It acts by potentiating GABAA (γ-aminobutyric acid type A) receptors, but where it binds to this receptor is not known and has been a matter of some debate. We synthesized a new propofol analog photolabeling reagent whose biological...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1340

    authors: Yip GM,Chen ZW,Edge CJ,Smith EH,Dickinson R,Hohenester E,Townsend RR,Fuchs K,Sieghart W,Evers AS,Franks NP

    更新日期:2013-11-01 00:00:00

  • YcaO domains use ATP to activate amide backbones during peptide cyclodehydrations.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio.944

    authors: Dunbar KL,Melby JO,Mitchell DA

    更新日期:2012-04-22 00:00:00

  • Phosphate release in F1-ATPase catalytic cycle follows ADP release.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio.443

    authors: Watanabe R,Iino R,Noji H

    更新日期:2010-11-01 00:00:00

  • Expanding chemical biology of 2-oxoglutarate oxygenases.

    abstract::Beyond established roles in collagen biosynthesis, hypoxic signaling and fatty acid metabolism, recent reports have now revealed roles for human 2-oxoglutarate-dependent oxygenases in histone and nucleic acid demethylation and in signaling protein hydroxylation. The emerging role of these oxygenases in enabling a mult...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio0308-152

    authors: Loenarz C,Schofield CJ

    更新日期:2008-03-01 00:00:00

  • A carbonate-forming Baeyer-Villiger monooxygenase.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio.1527

    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

  • Electron handoff.

    abstract:: ...

    journal_title:Nature chemical biology

    pub_type: 评论,杂志文章

    doi:10.1038/s41589-018-0073-9

    authors: Deane C

    更新日期:2018-06-01 00:00:00

  • Brain endogenous liver X receptor ligands selectively promote midbrain neurogenesis.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio.1156

    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

  • Discovery of a selective inhibitor of doublecortin like kinase 1.

    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

    pub_type: 杂志文章

    doi:10.1038/s41589-020-0506-0

    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

  • Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases.

    abstract::Thiolutin is a disulfide-containing antibiotic and anti-angiogenic compound produced by Streptomyces. Its biological targets are not known. We show that reduced thiolutin is a zinc chelator that inhibits the JAB1/MPN/Mov34 (JAMM) domain-containing metalloprotease Rpn11, a deubiquitinating enzyme of the 19S proteasome....

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.2370

    authors: Lauinger L,Li J,Shostak A,Cemel IA,Ha N,Zhang Y,Merkl PE,Obermeyer S,Stankovic-Valentin N,Schafmeier T,Wever WJ,Bowers AA,Carter KP,Palmer AE,Tschochner H,Melchior F,Deshaies RJ,Brunner M,Diernfellner A

    更新日期:2017-07-01 00:00:00

  • A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio.2070

    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

  • Grand challenge commentary: RNA epigenetics?

    abstract::Post-transcriptional RNA modifications can be dynamic and might have functions beyond fine-tuning the structure and function of RNA. Understanding these RNA modification pathways and their functions may allow researchers to identify new layers of gene regulation at the RNA level. ...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.482

    authors: He C

    更新日期:2010-12-01 00:00:00

  • Structural landscape of isolated agonist-binding domains from single AMPA receptors.

    abstract::AMPA receptors mediate fast excitatory neurotransmission by converting chemical signals into electrical signals, and thus it is important to understand the relationship between their chemical biology and their function. We used single-molecule fluorescence resonance energy transfer to examine the conformations explore...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.523

    authors: Landes CF,Rambhadran A,Taylor JN,Salatan F,Jayaraman V

    更新日期:2011-03-01 00:00:00

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

    abstract::ADP-ribosylation (ADPr) is a biologically and clinically important post-translational modification, but little is known about the amino acids it targets on cellular proteins. Here we present a proteomic approach for direct in vivo identification and quantification of ADPr sites on histones. We have identified 12 uniqu...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.2180

    authors: Leidecker O,Bonfiglio JJ,Colby T,Zhang Q,Atanassov I,Zaja R,Palazzo L,Stockum A,Ahel I,Matic I

    更新日期:2016-12-01 00:00:00

  • An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio.1816

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

    更新日期:2015-07-01 00:00:00

  • Eukaryotic DNA polymerases require an iron-sulfur cluster for the formation of active complexes.

    abstract::The eukaryotic replicative DNA polymerases (Pol α, δ and ɛ) and the major DNA mutagenesis enzyme Pol ζ contain two conserved cysteine-rich metal-binding motifs (CysA and CysB) in the C-terminal domain (CTD) of their catalytic subunits. Here we demonstrate by in vivo and in vitro approaches the presence of an essential...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.721

    authors: Netz DJ,Stith CM,Stümpfig M,Köpf G,Vogel D,Genau HM,Stodola JL,Lill R,Burgers PM,Pierik AJ

    更新日期:2011-11-27 00:00:00

  • Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio.1563

    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

  • N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation.

    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

    pub_type: 杂志文章

    doi:10.1038/s41589-018-0184-3

    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

  • A bridge between chemistry and biology.

    abstract::Chemical biology is an interdisciplinary field that is undergoing rapid expansion around the globe. Recently, the Japanese Society for Chemical Biology sponsored its inaugural scientific meeting to discuss research at the interface of chemistry and biology. ...

    journal_title:Nature chemical biology

    pub_type:

    doi:10.1038/nchembio0806-392

    authors: Kikuchi K,Kakeya H

    更新日期:2006-08-01 00:00:00

  • Phosphorylated glycosphingolipids essential for cholesterol mobilization in Caenorhabditis elegans.

    abstract::The nematode Caenorhabditis elegans requires exogenous cholesterol to survive and its depletion leads to early developmental arrest. Thus, tight regulation of cholesterol storage and distribution within the organism is indispensable. Here, we present a novel class of C. elegans phosphorylated glycosphingolipids, phosp...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.2347

    authors: Boland S,Schmidt U,Zagoriy V,Sampaio JL,Fritsche RF,Czerwonka R,Lübken T,Reimann J,Penkov S,Knölker HJ,Kurzchalia TV

    更新日期:2017-06-01 00:00:00

  • Allosteric inhibition of kinesin-5 modulates its processive directional motility.

    abstract::Small-molecule inhibitors of kinesin-5 (refs. 1-3), a protein essential for eukaryotic cell division, represent alternatives to antimitotic agents that target tubulin. While tubulin is needed for multiple intracellular processes, the known functions of kinesin-5 are limited to dividing cells, making it likely that kin...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio812

    authors: Kwok BH,Kapitein LC,Kim JH,Peterman EJ,Schmidt CF,Kapoor TM

    更新日期:2006-09-01 00:00:00

  • Identification of G-quadruplexes in long functional RNAs using 7-deazaguanine RNA.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio.2228

    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

  • Coordination of auxin and ethylene biosynthesis by the aminotransferase VAS1.

    abstract::We identify an Arabidopsis pyridoxal-phosphate-dependent aminotransferase, VAS1, whose loss-of-function simultaneously increases amounts of the phytohormone auxin and the ethylene precursor 1-aminocyclopropane-1-carboxylate. VAS1 uses the ethylene biosynthetic intermediate methionine as an amino donor and the auxin bi...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1178

    authors: Zheng Z,Guo Y,Novák O,Dai X,Zhao Y,Ljung K,Noel JP,Chory J

    更新日期:2013-04-01 00:00:00

  • Diels-Alder reaction-triggered bioorthogonal protein decaging in living cells.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio.1656

    authors: Li J,Jia S,Chen PR

    更新日期:2014-12-01 00:00:00

  • Targeting virulence: a new paradigm for antimicrobial therapy.

    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

    pub_type: 杂志文章,评审

    doi:10.1038/nchembio.2007.24

    authors: Clatworthy AE,Pierson E,Hung DT

    更新日期:2007-09-01 00:00:00

  • Light-activated chemical probing of nucleobase solvent accessibility inside cells.

    abstract::The discovery of functional RNAs that are critical for normal and disease physiology continues to expand at a breakneck pace. Many RNA functions are controlled by the formation of specific structures, and an understanding of each structural component is necessary to elucidate its function. Measuring solvent accessibil...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.2548

    authors: Feng C,Chan D,Joseph J,Muuronen M,Coldren WH,Dai N,Corrêa IR Jr,Furche F,Hadad CM,Spitale RC

    更新日期:2018-03-01 00:00:00