Structure and function of the bacterial decapping enzyme NudC.

Abstract:

:RNA capping and decapping are thought to be distinctive features of eukaryotes. The redox cofactor NAD was recently discovered to be attached to small regulatory RNAs in bacteria in a cap-like manner, and Nudix hydrolase NudC was found to act as a NAD-decapping enzyme in vitro and in vivo. Here, crystal structures of Escherichia coli NudC in complex with substrate NAD and with cleavage product NMN reveal the catalytic residues lining the binding pocket and principles underlying molecular recognition of substrate and product. Biochemical mutation analysis identifies the conserved Nudix motif as the catalytic center of the enzyme, which needs to be homodimeric, as the catalytic pocket is composed of amino acids from both monomers. NudC is single-strand specific and has a purine preference for the 5'-terminal nucleotide. The enzyme strongly prefers NAD-linked RNA (NAD-RNA) over NAD and binds to a diverse set of cellular RNAs in an unspecific manner.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Höfer K,Li S,Abele F,Frindert J,Schlotthauer J,Grawenhoff J,Du J,Patel DJ,Jäschke A

doi

10.1038/nchembio.2132

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

730-4

issue

9

eissn

1552-4450

issn

1552-4469

pii

nchembio.2132

journal_volume

12

pub_type

杂志文章
  • N6-mA condenses chromatin.

    abstract:: ...

    journal_title:Nature chemical biology

    pub_type: 评论,杂志文章

    doi:10.1038/s41589-018-0199-9

    authors: Song Y

    更新日期:2019-01-01 00:00:00

  • Using the pimeloyl-CoA synthetase adenylation fold to synthesize fatty acid thioesters.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio.2361

    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

  • Unifying principles of bifunctional, proximity-inducing small molecules.

    abstract::Nature uses a variety of tools to mediate the flow of information in cells, many of which control distances between key biomacromolecules. Researchers have thus generated compounds whose activities stem from interactions with two (or more) proteins simultaneously. In this Perspective, we describe how these 'bifunction...

    journal_title:Nature chemical biology

    pub_type: 杂志文章,评审

    doi:10.1038/s41589-020-0469-1

    authors: Gerry CJ,Schreiber SL

    更新日期:2020-04-01 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

  • Essential nontranslational functions of tRNA synthetases.

    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

    pub_type: 杂志文章,评审

    doi:10.1038/nchembio.1158

    authors: Guo M,Schimmel P

    更新日期:2013-03-01 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

  • 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

  • Small-molecule WNK inhibition regulates cardiovascular and renal function.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio.2168

    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

  • ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio.2239

    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

  • The nongenotoxic carcinogens naphthalene and para-dichlorobenzene suppress apoptosis in Caenorhabditis elegans.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio791

    authors: Kokel D,Li Y,Qin J,Xue D

    更新日期:2006-06-01 00:00:00

  • Druggable sensors of the unfolded protein response.

    abstract::The inability of cells to properly fold, modify and assemble secretory and transmembrane proteins leads to accumulation of misfolded proteins in the endoplasmic reticulum (ER). Under these conditions of 'ER stress', cell survival depends on homeostatic benefits from an intracellular signaling pathway called the unfold...

    journal_title:Nature chemical biology

    pub_type: 杂志文章,评审

    doi:10.1038/nchembio.1664

    authors: Maly DJ,Papa FR

    更新日期:2014-11-01 00:00:00

  • Versatility of biological non-heme Fe(II) centers in oxygen activation reactions.

    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

    pub_type: 杂志文章,评审

    doi:10.1038/nchembio.71

    authors: Kovaleva EG,Lipscomb JD

    更新日期:2008-03-01 00:00:00

  • 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 remai...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.2127

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

    更新日期:2016-09-01 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

  • 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

  • Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine.

    abstract::Nitric oxide (NO) signaling through the formation of cGMP is well established; however, there seems to be an increasing role for cGMP-independent NO signaling. Although key molecular details remain unanswered, S-nitrosation represents an example of cGMP-independent NO signaling. This modification has garnered recent a...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio720

    authors: Mitchell DA,Marletta MA

    更新日期:2005-08-01 00:00:00

  • Behind the folding funnel diagram.

    abstract::This Commentary clarifies the meaning of the funnel diagram, which has been widely cited in papers on protein folding. To aid in the analysis of the funnel diagram, this Commentary reviews historical approaches to understanding the mechanism of protein folding. The primary role of free energy in protein folding is dis...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.565

    authors: Karplus M

    更新日期:2011-06-17 00:00:00

  • A new mechanism of allostery in a G protein-coupled receptor dimer.

    abstract::SB269652 is to our knowledge the first drug-like allosteric modulator of the dopamine D2 receptor (D2R), but it contains structural features associated with orthosteric D2R antagonists. Using a functional complementation system to control the identity of individual protomers within a dimeric D2R complex, we converted ...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1593

    authors: Lane JR,Donthamsetti P,Shonberg J,Draper-Joyce CJ,Dentry S,Michino M,Shi L,López L,Scammells PJ,Capuano B,Sexton PM,Javitch JA,Christopoulos A

    更新日期:2014-09-01 00:00:00

  • Symbiosis in chemistry and biology.

    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

    pub_type:

    doi:10.1038/nchembio0206-59

    authors: Murphy PV,Rutledge PJ

    更新日期:2006-02-01 00:00:00

  • Cdk5 induces constitutive activation of 5-HT6 receptors to promote neurite growth.

    abstract::The serotonin6 receptor (5-HT6R) is a promising target for treating cognitive deficits of schizophrenia often linked to alterations of neuronal development. This receptor controls neurodevelopmental processes, but the signaling mechanisms involved remain poorly understood. Using a proteomic strategy, we show that 5-HT...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1547

    authors: Duhr F,Déléris P,Raynaud F,Séveno M,Morisset-Lopez S,Mannoury la Cour C,Millan MJ,Bockaert J,Marin P,Chaumont-Dubel S

    更新日期:2014-07-01 00:00:00

  • Nascent peptide assists the ribosome in recognizing chemically distinct small molecules.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio.1998

    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

  • GATOR1 regulates nitrogenic cataplerotic reactions of the mitochondrial TCA cycle.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio.2478

    authors: Chen J,Sutter BM,Shi L,Tu BP

    更新日期:2017-11-01 00:00:00

  • A chemical inhibitor of jasmonate signaling targets JAR1 in Arabidopsis thaliana.

    abstract::Jasmonates are lipid-derived plant hormones that regulate plant defenses and numerous developmental processes. Although the biosynthesis and molecular function of the most active form of the hormone, (+)-7-iso-jasmonoyl-L-isoleucine (JA-Ile), have been unraveled, it remains poorly understood how the diversity of bioac...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1591

    authors: Meesters C,Mönig T,Oeljeklaus J,Krahn D,Westfall CS,Hause B,Jez JM,Kaiser M,Kombrink E

    更新日期:2014-10-01 00:00:00

  • A predictive model for drug bioaccumulation and bioactivity in Caenorhabditis elegans.

    abstract::The resistance of Caenorhabditis elegans to pharmacological perturbation limits its use as a screening tool for novel small bioactive molecules. One strategy to improve the hit rate of small-molecule screens is to preselect molecules that have an increased likelihood of reaching their target in the worm. To learn whic...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.380

    authors: Burns AR,Wallace IM,Wildenhain J,Tyers M,Giaever G,Bader GD,Nislow C,Cutler SR,Roy PJ

    更新日期:2010-07-01 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

  • Tracking single molecules at work in living cells.

    abstract::Methods for imaging and tracking single molecules conjugated with fluorescent probes, called single-molecule tracking (SMT), are now providing researchers with the unprecedented ability to directly observe molecular behaviors and interactions in living cells. Current SMT methods are achieving almost the ultimate spati...

    journal_title:Nature chemical biology

    pub_type: 杂志文章,评审

    doi:10.1038/nchembio.1558

    authors: Kusumi A,Tsunoyama TA,Hirosawa KM,Kasai RS,Fujiwara TK

    更新日期:2014-07-01 00:00:00

  • Engineering protein stability with atomic precision in a monomeric miniprotein.

    abstract::Miniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPα-Tyr, a designed peptide comprising an α-helix buttressed by a polyproline II helix. PPα-Tyr is water soluble and monomeric, and it unfolds cooperatively with a midpoint unfolding...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.2380

    authors: Baker EG,Williams C,Hudson KL,Bartlett GJ,Heal JW,Porter Goff KL,Sessions RB,Crump MP,Woolfson DN

    更新日期:2017-07-01 00:00:00

  • Dynamic polymorphism of single actin molecules in the actin filament.

    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

    pub_type: 杂志文章

    doi:10.1038/nchembio763

    authors: Kozuka J,Yokota H,Arai Y,Ishii Y,Yanagida T

    更新日期:2006-02-01 00:00:00

  • Completing the uric acid degradation pathway through phylogenetic comparison of whole genomes.

    abstract::Mammals that degrade uric acid are not affected by gout or urate kidney stones. It is not fully understood how they convert uric acid into the much more soluble allantoin. Until recently, it had long been thought that urate oxidase was the only enzyme responsible for this conversion. However, detailed studies of the m...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio768

    authors: Ramazzina I,Folli C,Secchi A,Berni R,Percudani R

    更新日期:2006-03-01 00:00:00

  • How proteins bind macrocycles.

    abstract::The potential utility of synthetic macrocycles (MCs) as drugs, particularly against low-druggability targets such as protein-protein interactions, has been widely discussed. There is little information, however, to guide the design of MCs for good target protein-binding activity or bioavailability. To address this kno...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1584

    authors: Villar EA,Beglov D,Chennamadhavuni S,Porco JA Jr,Kozakov D,Vajda S,Whitty A

    更新日期:2014-09-01 00:00:00