当前位置： SCI文献检索 > NATURE STRUCTURAL & MOLECULAR BIOLOGY期刊下所有文献 > A phospho-BAD BH3 helix activates glucokinase by a mechanism distinct from that of allosteric activators.

A phospho-BAD BH3 helix activates glucokinase by a mechanism distinct from that of allosteric activators.

Abstract：

:Glucokinase (GK) is a glucose-phosphorylating enzyme that regulates insulin release and hepatic metabolism, and its loss of function is implicated in diabetes pathogenesis. GK activators (GKAs) are attractive therapeutics in diabetes; however, clinical data indicate that their benefits can be offset by hypoglycemia, owing to marked allosteric enhancement of the enzyme's glucose affinity. We show that a phosphomimetic of the BCL-2 homology 3 (BH3) α-helix derived from human BAD, a GK-binding partner, increases the enzyme catalytic rate without dramatically changing glucose affinity, thus providing a new mechanism for pharmacologic activation of GK. Remarkably, BAD BH3 phosphomimetic mediates these effects by engaging a new region near the enzyme's active site. This interaction increases insulin secretion in human islets and restores the function of naturally occurring human GK mutants at the active site. Thus, BAD phosphomimetics may serve as a new class of GKAs.

journal_name

Nat Struct Mol Biol

journal_title

Nature structural & molecular biology

authors

Szlyk B,Braun CR,Ljubicic S,Patton E,Bird GH,Osundiji MA,Matschinsky FM,Walensky LD,Danial NN

doi

10.1038/nsmb.2717

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

36-42

issue

1

eissn

1545-9993

issn

1545-9985

pii

nsmb.2717

journal_volume

21

pub_type

杂志文章

相关文献

NATURE STRUCTURAL & MOLECULAR BIOLOGY文献大全
  • Molecular basis of histone H3K36me3 recognition by the PWWP domain of Brpf1.

    abstract：:Trimethylation of Lys36 in histone H3 (H3K36me3) coordinates events associated with the elongation phase of transcription and is also emerging as an important epigenetic regulator of cell growth and differentiation. We have identified the PWWP domain of bromo and plant homeodomain (PHD) finger-containing protein 1 (BR...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.1797

    authors： Vezzoli A,Bonadies N,Allen MD,Freund SM,Santiveri CM,Kvinlaug BT,Huntly BJ,Göttgens B,Bycroft M

    更新日期：2010-05-01 00:00:00

  • TRF2 binds branched DNA to safeguard telomere integrity.

    abstract：:Although t-loops protect telomeres, they are at risk of cleavage by Holliday junction (HJ) resolvases if branch migration converts the three-way t-loop junction into four-way HJs. T-loop cleavage is repressed by the TRF2 basic domain, which binds three- and four-way junctions and protects HJs in vitro. By replacing th...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.3451

    authors： Schmutz I,Timashev L,Xie W,Patel DJ,de Lange T

    更新日期：2017-09-01 00:00:00

  • Structural basis of the proinflammatory signaling complex mediated by TSLP.

    abstract：:Thymic stromal lymphopoietin (TSLP), a cytokine produced by epithelial cells at barrier surfaces, is pivotal for the development of widespread chronic inflammatory disorders such as asthma and atopic dermatitis. The structure of the mouse TSLP-mediated signaling complex reveals how TSLP establishes extensive interface...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.2794

    authors： Verstraete K,van Schie L,Vyncke L,Bloch Y,Tavernier J,Pauwels E,Peelman F,Savvides SN

    更新日期：2014-04-01 00:00:00

  • Efficiency and specificity in microRNA biogenesis.

    abstract：:Primary microRNA cleavage by the Drosha-Dgcr8 'Microprocessor' complex is critical for microRNA biogenesis. Yet, the Microprocessor may also cleave other nuclear RNAs in a nonspecific manner. We studied Microprocessor function using mathematical modeling and experiments in mouse and human tissues. We found that the au...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.2293

    authors： Barad O,Mann M,Chapnik E,Shenoy A,Blelloch R,Barkai N,Hornstein E

    更新日期：2012-05-13 00:00:00

  • BAK core dimers bind lipids and can be bridged by them.

    abstract：:BAK and BAX are essential mediators of apoptosis that oligomerize in response to death cues, thereby causing permeabilization of the mitochondrial outer membrane. Their transition from quiescent monomers to pore-forming oligomers involves a well-characterized symmetric dimer intermediate. However, no essential seconda...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/s41594-020-0494-5

    authors： Cowan AD,Smith NA,Sandow JJ,Kapp EA,Rustam YH,Murphy JM,Brouwer JM,Bernardini JP,Roy MJ,Wardak AZ,Tan IK,Webb AI,Gulbis JM,Smith BJ,Reid GE,Dewson G,Colman PM,Czabotar PE

    更新日期：2020-11-01 00:00:00

  • Synaptic vesicle fusion.

    abstract：:The core of the neurotransmitter release machinery is formed by SNARE complexes, which bring the vesicle and plasma membranes together and are key for fusion, and by Munc18-1, which controls SNARE-complex formation and may also have a direct role in fusion. In addition, SNARE complex assembly is likely orchestrated by...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章,评审

    doi：10.1038/nsmb.1450

    authors： Rizo J,Rosenmund C

    更新日期：2008-07-01 00:00:00

  • Ancestral-sequence reconstruction unveils the structural basis of function in mammalian FMOs.

    abstract：:Flavin-containing monooxygenases (FMOs) are ubiquitous in all domains of life and metabolize a myriad of xenobiotics, including toxins, pesticides and drugs. However, despite their pharmacological importance, structural information remains bereft. To further our understanding behind their biochemistry and diversity, w...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/s41594-019-0347-2

    authors： Nicoll CR,Bailleul G,Fiorentini F,Mascotti ML,Fraaije MW,Mattevi A

    更新日期：2020-01-01 00:00:00

  • Structure of full-length human anti-PD1 therapeutic IgG4 antibody pembrolizumab.

    abstract：:Immunoglobulin G4 antibodies exhibit unusual properties with important biological consequences. We report the structure of the human full-length IgG4 S228P anti-PD1 antibody pembrolizumab, solved to 2.3-Å resolution. Pembrolizumab is a compact molecule, consistent with the presence of a short hinge region. The Fc doma...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.3129

    authors： Scapin G,Yang X,Prosise WW,McCoy M,Reichert P,Johnston JM,Kashi RS,Strickland C

    更新日期：2015-12-01 00:00:00

  • Author Correction: Quantifying the dynamics of IRES and cap translation with single-molecule resolution in live cells.

    abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title：Nature structural & molecular biology

    pub_type： 已发布勘误

    doi：10.1038/s41594-020-00531-z

    authors： Koch A,Aguilera L,Morisaki T,Munsky B,Stasevich TJ

    更新日期：2020-12-01 00:00:00

  • Direct observation of the myosin-Va power stroke and its reversal.

    abstract：:Complex forms of cellular motility, including cell division, organelle trafficking or signal amplification in the auditory system, require strong coordination of the myosin motors involved. The most basic mechanism of coordination is via direct mechanical interactions of individual motor heads leading to modification ...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.1820

    authors： Sellers JR,Veigel C

    更新日期：2010-05-01 00:00:00

  • Nuclear pore formation but not nuclear growth is governed by cyclin-dependent kinases (Cdks) during interphase.

    abstract：:Nuclear volume and the number of nuclear pore complexes (NPCs) on the nucleus almost double during interphase in dividing cells. How these events are coordinated with the cell cycle is poorly understood, particularly in mammalian cells. We report here, based on newly developed techniques for visualizing NPC formation,...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.1878

    authors： Maeshima K,Iino H,Hihara S,Funakoshi T,Watanabe A,Nishimura M,Nakatomi R,Yahata K,Imamoto F,Hashikawa T,Yokota H,Imamoto N

    更新日期：2010-09-01 00:00:00

  • Author Correction: A gel phase promotes condensation of liquid P granules in Caenorhabditis elegans embryos.

    abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title：Nature structural & molecular biology

    pub_type： 已发布勘误

    doi：10.1038/s41594-019-0367-y

    authors： Putnam A,Cassani M,Smith J,Seydoux G

    更新日期：2020-02-01 00:00:00

  • Multiple functions of MRN in end-joining pathways during isotype class switching.

    abstract：:The Mre11-Rad50-NBS1 (MRN) complex has many roles in response to DNA double-strand breaks, but its functions in repair by nonhomologous end joining (NHEJ) pathways are poorly understood. We have investigated requirements for MRN in class switch recombination (CSR), a programmed DNA rearrangement in B lymphocytes that ...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.1639

    authors： Dinkelmann M,Spehalski E,Stoneham T,Buis J,Wu Y,Sekiguchi JM,Ferguson DO

    更新日期：2009-08-01 00:00:00

  • Author Correction: H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming.

    abstract：:In this article, the Ponceau staining presented in Fig. 1b (right, bottom) does not follow best practices for figure preparation since itinadvertently included duplications from the Ponceau staining presented in Supplementary Fig. 1b (for which the same preparation ofnucleosomes from HeLa cells had been used). A new F...

    journal_title：Nature structural & molecular biology

    pub_type： 已发布勘误

    doi：10.1038/s41594-018-0090-0

    authors： Daujat S,Weiss T,Mohn F,Lange UC,Ziegler-Birling C,Zeissler U,Lappe M,Schübeler D,Torres-Padilla ME,Schneider R

    更新日期：2018-08-01 00:00:00

  • Translational control of the cytosolic stress response by mitochondrial ribosomal protein L18.

    abstract：:In response to stress, cells attenuate global protein synthesis but permit efficient translation of mRNAs encoding heat-shock proteins (HSPs). Although decades have passed since the first description of the heat-shock response, how cells achieve translational control of HSP synthesis remains enigmatic. Here we report ...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.3010

    authors： Zhang X,Gao X,Coots RA,Conn CS,Liu B,Qian SB

    更新日期：2015-05-01 00:00:00

  • Regulation of microRNA-mediated gene silencing by microRNA precursors.

    abstract：:Processing of microRNAs (miRNAs) from their precursors to their biologically active mature forms is regulated during development and cancer. We show that mouse pri- or pre-miR-151 can bind to and compete with mature miR-151-5p and miR-151-3p for binding sites contained within the complementary regions of the E2f6 mRNA...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.2862

    authors： Roy-Chaudhuri B,Valdmanis PN,Zhang Y,Wang Q,Luo QJ,Kay MA

    更新日期：2014-09-01 00:00:00

  • Methylation of H4 lysines 5, 8 and 12 by yeast Set5 calibrates chromatin stress responses.

    abstract：:Methylation of histones is central to chromatin regulation, and thus previously unknown mechanisms regulating genome function can be revealed through the discovery of new histone methyl marks. Here we identify Set5 as the first histone H4 methyltransferase, which monomethylates the critical H4 lysine residues 5, 8 and...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.2252

    authors： Green EM,Mas G,Young NL,Garcia BA,Gozani O

    更新日期：2012-02-19 00:00:00

  • Mapping the sequence of conformational changes underlying selectivity filter gating in the K(v)11.1 potassium channel.

    abstract：:The potassium channel selectivity filter both discriminates between K(+) and sodium ions and contributes to gating of ion flow. Static structures of conducting (open) and nonconducting (inactivated) conformations of this filter are known; however, the sequence of protein rearrangements that connect these two states is...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.1966

    authors： Wang DT,Hill AP,Mann SA,Tan PS,Vandenberg JI

    更新日期：2011-01-01 00:00:00

  • Transcription shapes DNA replication initiation and termination in human cells.

    abstract：:Although DNA replication is a fundamental aspect of biology, it is not known what determines where DNA replication starts and stops in the human genome. We directly identified and quantitatively compared sites of replication initiation and termination in untransformed human cells. We found that replication preferentia...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/s41594-018-0171-0

    authors： Chen YH,Keegan S,Kahli M,Tonzi P,Fenyö D,Huang TT,Smith DJ

    更新日期：2019-01-01 00:00:00

  • Quantification of translation uncovers the functions of the alternative transcriptome.

    abstract：:Translation has a fundamental function in defining the fate of the transcribed genome. RNA-sequencing (RNA-seq) data enable the quantification of complex transcript mixtures, often detecting several transcript isoforms of unknown functions for one gene. Here, we describe ORFquant, a method to annotate and quantify tra...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/s41594-020-0450-4

    authors： Calviello L,Hirsekorn A,Ohler U

    更新日期：2020-08-01 00:00:00

  • Autoinhibition of X11/Mint scaffold proteins revealed by the closed conformation of the PDZ tandem.

    abstract：:Members of the X11/Mint family of multidomain adaptor proteins are composed of a divergent N terminus, a conserved PTB domain and a pair of C-terminal PDZ domains. Many proteins can interact with the PDZ tandem of X11 proteins, although the mechanism of such interactions is unclear. Here we show that the highly conser...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb958

    authors： Long JF,Feng W,Wang R,Chan LN,Ip FC,Xia J,Ip NY,Zhang M

    更新日期：2005-08-01 00:00:00

  • A potent and highly specific FN3 monobody inhibitor of the Abl SH2 domain.

    abstract：:Interactions between Src homology 2 (SH2) domains and phosphotyrosine sites regulate tyrosine kinase signaling networks. Selective perturbation of these interactions is challenging due to the high homology among the 120 human SH2 domains. Using an improved phage-display selection system, we generated a small antibody ...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.1793

    authors： Wojcik J,Hantschel O,Grebien F,Kaupe I,Bennett KL,Barkinge J,Jones RB,Koide A,Superti-Furga G,Koide S

    更新日期：2010-04-01 00:00:00

  • The E3 ligase RNF8 regulates KU80 removal and NHEJ repair.

    abstract：:The ubiquitination cascade has a key role in the assembly of repair and signaling proteins at sites of double-strand DNA breaks. The E3 ubiquitin ligase RING finger protein 8 (RNF8) triggers the initial ubiquitination at double-strand DNA breaks, whereas sustained ubiquitination requires the downstream E3 ligase RING ...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.2211

    authors： Feng L,Chen J

    更新日期：2012-01-22 00:00:00

  • Long noncoding RNA LINP1 regulates repair of DNA double-strand breaks in triple-negative breast cancer.

    abstract：:Long noncoding RNAs (lncRNAs) play critical roles during tumorigenesis by functioning as scaffolds that regulate protein-protein, protein-DNA or protein-RNA interactions. Using a clinically guided genetic screening approach, we identified lncRNA in nonhomologous end joining (NHEJ) pathway 1 (LINP1), which is overexpre...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.3211

    authors： Zhang Y,He Q,Hu Z,Feng Y,Fan L,Tang Z,Yuan J,Shan W,Li C,Hu X,Tanyi JL,Fan Y,Huang Q,Montone K,Dang CV,Zhang L

    更新日期：2016-06-01 00:00:00

  • Structural changes in a marine podovirus associated with release of its genome into Prochlorococcus.

    abstract：:Podovirus P-SSP7 infects Prochlorococcus marinus, the most abundant oceanic photosynthetic microorganism. Single-particle cryo-electron microscopy yields icosahedral and asymmetrical structures of infectious P-SSP7 with 4.6-A and 9-A resolution, respectively. The asymmetric reconstruction reveals how symmetry mismatch...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.1823

    authors： Liu X,Zhang Q,Murata K,Baker ML,Sullivan MB,Fu C,Dougherty MT,Schmid MF,Osburne MS,Chisholm SW,Chiu W

    更新日期：2010-07-01 00:00:00

  • Interaction between the keratin cytoskeleton and eEF1Bgamma affects protein synthesis in epithelial cells.

    abstract：:Eukaryotic elongation factor-1 (eEF1) is essential for peptide-chain elongation during translation. We report that its gamma subunit (eEF1Bgamma) specifically binds, and bundles, keratin intermediate filaments. Disrupting this interaction depresses translation by approximately 20% and selectively increases 80S ribosom...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb1301

    authors： Kim S,Kellner J,Lee CH,Coulombe PA

    更新日期：2007-10-01 00:00:00

  • Misregulation of miR-1 processing is associated with heart defects in myotonic dystrophy.

    abstract：:Myotonic dystrophy is an RNA gain-of-function disease caused by expanded CUG or CCUG repeats, which sequester the RNA binding protein MBNL1. Here we describe a newly discovered function for MBNL1 as a regulator of pre-miR-1 biogenesis and find that miR-1 processing is altered in heart samples from people with myotonic...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.2067

    authors： Rau F,Freyermuth F,Fugier C,Villemin JP,Fischer MC,Jost B,Dembele D,Gourdon G,Nicole A,Duboc D,Wahbi K,Day JW,Fujimura H,Takahashi MP,Auboeuf D,Dreumont N,Furling D,Charlet-Berguerand N

    更新日期：2011-06-19 00:00:00

  • A processed noncoding RNA regulates an altruistic bacterial antiviral system.

    abstract：:The ≥ 10³⁰ bacteriophages on Earth relentlessly drive adaptive coevolution, forcing the generation of protective mechanisms in their bacterial hosts. One such bacterial phage-resistance system, ToxIN, consists of a protein toxin (ToxN) that is inhibited in vivo by a specific RNA antitoxin (ToxI); however, the mechanis...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.1981

    authors： Blower TR,Pei XY,Short FL,Fineran PC,Humphreys DP,Luisi BF,Salmond GP

    更新日期：2011-02-01 00:00:00

  • Defining the landscape of ATP-competitive inhibitor resistance residues in protein kinases.

    abstract：:Kinases are involved in disease development and modulation of their activity can be therapeutically beneficial. Drug-resistant mutant kinases are valuable tools in drug discovery efforts, but the prediction of mutants across the kinome is challenging. Here, we generate deep mutational scanning data to identify mutant ...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/s41594-019-0358-z

    authors： Persky NS,Hernandez D,Do Carmo M,Brenan L,Cohen O,Kitajima S,Nayar U,Walker A,Pantel S,Lee Y,Cordova J,Sathappa M,Zhu C,Hayes TK,Ram P,Pancholi P,Mikkelsen TS,Barbie DA,Yang X,Haq R,Piccioni F,Root DE,Johannes

    更新日期：2020-01-01 00:00:00

  • Structural basis for the recognition of N-end rule substrates by the UBR box of ubiquitin ligases.

    abstract：:The N-end rule pathway is a regulated proteolytic system that targets proteins containing destabilizing N-terminal residues (N-degrons) for ubiquitination and proteasomal degradation in eukaryotes. The N-degrons of type 1 substrates contain an N-terminal basic residue that is recognized by the UBR box domain of the E3...

    journal_title：Nature structural & molecular biology

    pub_type： 杂志文章

    doi：10.1038/nsmb.1907

    authors： Choi WS,Jeong BC,Joo YJ,Lee MR,Kim J,Eck MJ,Song HK

    更新日期：2010-10-01 00:00:00