ChemBioChem

Cover image for Vol. 14 Issue 15

October 11, 2013

Volume 14, Issue 15

Pages 1909–2058

  1. Cover Pictures

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. Corrigendum
    5. News
    6. Highlights
    7. Communications
    8. Full Papers
    1. You have free access to this content
      Cover Picture: Defining a Substrate-Binding Model of a Polysialyltransferase (ChemBioChem 15/2013) (page 1909)

      Dr. Friedrich Freiberger, Raphael Böhm, Dr. David Schwarzer, Prof. Dr. Rita Gerardy-Schahn, Dr. Thomas Haselhorst and Prof. Dr. Mark von Itzstein

      Version of Record online: 7 OCT 2013 | DOI: 10.1002/cbic.201390054

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      The cover picture shows the proposed PolySia acceptor and CMP-Neu5Ac binding model of Neisseria meningitidis (Nm) polysialyltransferase (foreground) and Nm bacteria adhering to a cell surface (background). The polySia acceptor binding site is located within the first Rossmann domain and accommodates at least six Sia acceptor residues. The CMP-Sia donor binding site is located within the second Rossmann domain. The key amino acid residues involved in either donor recognition or enzyme catalysis—H278, S328, S329 and E153—were identified in the two Rossmann Domains. For further information, see the communication by T. Haselhorst, M. von Itzstein, et al. on p. 1949 ff.

    2. You have free access to this content
      Inside Cover: Rescue of Functional CFTR Channels in Cystic Fibrosis: A Dramatic Multivalent Effect Using Iminosugar Cluster-Based Correctors (ChemBioChem 15/2013) (page 1910)

      Prof. Philippe Compain, Camille Decroocq, Dr. Antoine Joosten, Julien de Sousa, Dr. David Rodríguez-Lucena, Prof. Terry D. Butters, Dr. Johanna Bertrand, Dr. Romain Clément, Clément Boinot, Prof. Frédéric Becq and Dr. Caroline Norez

      Version of Record online: 7 OCT 2013 | DOI: 10.1002/cbic.201390055

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      The inside cover picture shows a trivalent iminosugar as a powerful trident to target cystic fibrosis by rescuing mutant CFTR channels. This compound, displaying three copies of the clinical candidate miglustat, leads to a CFTR corrector that is superior by two orders of magnitude in efficiency. For more details, see the paper by P. Compain et al. on p. 2050 ff.

  2. Graphical Abstract

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. Corrigendum
    5. News
    6. Highlights
    7. Communications
    8. Full Papers
  3. Corrigendum

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. Corrigendum
    5. News
    6. Highlights
    7. Communications
    8. Full Papers
    1. You have free access to this content
      Corrigendum: Incorporation of Nucleoside Probes Opposite O6-Methylguanine by Sulfolobus solfataricus DNA Polymerase Dpo4: Importance of Hydrogen Bonding (page 1918)

      Alessia Stornetta, Dr. Todor Angelov, Prof. Dr. F. Peter Guengerich and Prof. Dr. Shana J. Sturla

      Version of Record online: 7 OCT 2013 | DOI: 10.1002/cbic.201300564

  4. News

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. Corrigendum
    5. News
    6. Highlights
    7. Communications
    8. Full Papers
  5. Highlights

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. Corrigendum
    5. News
    6. Highlights
    7. Communications
    8. Full Papers
    1. Picture Perfect: DNA-Templated Photoaffinity Labeling (pages 1927–1928)

      Dr. Sofia Barluenga and Prof. Nicolas Winssinger

      Version of Record online: 4 SEP 2013 | DOI: 10.1002/cbic.201300416

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      Just so far apart and no further: Small molecules target ID by DNA tagging. Nucleic acid hybridization has been used to pair a photo-crosslinking group with a small molecule of interest. Following photoactivation, the protein(s) interacting with the small molecule are covalently linked to a nucleic acid tag.

    2. “Rolling out” High-Molecular-Weight Proteins, which Contain Repeating Polypeptide Motif, by Using Rolling Circle Amplification (pages 1929–1930)

      Yue Zheng and Prof. Herman O. Sintim

      Version of Record online: 4 SEP 2013 | DOI: 10.1002/cbic.201300415

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      Keep going round in circles: On a circular mRNA template and without an end in sight, E. coli ribosomes have no option but to keep on making a high-molecular-weight polypeptide with repeating units. In this Highlight, the recently published work by Abe and co-workers on this topic is discussed.

  6. Communications

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. Corrigendum
    5. News
    6. Highlights
    7. Communications
    8. Full Papers
    1. Mechanochemical Properties of Individual Human Telomeric RNA (TERRA) G-Quadruplexes (pages 1931–1935)

      Philip M. Yangyuoru, Dr. Amy Y. Q. Zhang, Zhe Shi, Deepak Koirala, Prof. Shankar Balasubramanian and Dr. Hanbin Mao

      Version of Record online: 26 AUG 2013 | DOI: 10.1002/cbic.201300350

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      Potential functions: By following the unfolding and refolding of individual human RNA telomeric (TERRA) G-quadruplexes (GQs) in laser tweezers, the mechanical stability and transition kinetics of RNA GQs are obtained. Comparison between TERRA and DNA GQs suggests their different regulatory capacities for processes associated with human telomeres.

    2. Characterisation of CMP-Sialic Acid Transporter Substrate Recognition (pages 1936–1942)

      Dr. Andrea Maggioni, Prof. Mark von Itzstein, Ingrid Bibiana Rodríguez Guzmán, Dr. Angel Ashikov, Dr. Alexandre S. Stephens, Dr. Thomas Haselhorst and Dr. Joe Tiralongo

      Version of Record online: 6 SEP 2013 | DOI: 10.1002/cbic.201300298

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      CMP-sialic acid transporter: We report an in-depth, multidisciplinary, structural study that has identified the amino acid residues intimately involved in CMP-sialic acid transporter (CST) substrate specificity. Our data provide a significant contribution towards a better understanding the structure–function relationship of this important family of transporters and the rational design of CST inhibitors.

    3. The Cleavage Domain of the Amyloid Precursor Protein Transmembrane Helix Does Not Exhibit Above-Average Backbone Dynamics (pages 1943–1948)

      Oxana Pester, Alexander Götz, Prof. Dr. Gerd Multhaup, Dr. Christina Scharnagl and Prof. Dr. Dieter Langosch

      Version of Record online: 17 SEP 2013 | DOI: 10.1002/cbic.201300322

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      Wobbly backbone: The backbone dynamics of the amyloid precursor protein (APP) transmembrane helix was compared to those of other transmembrane domains. In contrast to expectation, no above-average backbone dynamics was found for the APP transmembrane helix; the dynamics thus appears not to be optimized for cleavage.

    4. Defining a Substrate-Binding Model of a Polysialyltransferase (pages 1949–1953)

      Dr. Friedrich Freiberger, Raphael Böhm, Dr. David Schwarzer, Prof. Dr. Rita Gerardy-Schahn, Dr. Thomas Haselhorst and Prof. Dr. Mark von Itzstein

      Version of Record online: 5 SEP 2013 | DOI: 10.1002/cbic.201300367

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      Highly disciplined transfers: Polysialyltransferases are important enzymes responsible for the biosynthesis of α-linked polysialic acids. We used a multidisciplinary approach, and propose the first substrate-binding model for a bacterial polysialyltransferase. Furthermore, we identify key amino acid residues involved in catalysis.

    5. Single-Molecule Unzipping Force Analysis of HU–DNA Complexes (pages 1954–1957)

      Dr. Remus T. Dame, Dr. Michael A. Hall and Dr. Michelle D. Wang

      Version of Record online: 2 SEP 2013 | DOI: 10.1002/cbic.201300413

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      Road block: Mechanical unzipping of double-stranded DNA yields a sequence-dependent unzipping force landscape. We have used optical tweezers to unzip dsDNA and investigate the effect of the abundant nucleoid-associated protein HU on the unzipping force landscape.

    6. Selective Functionalization of the Protein N Terminus with N-Myristoyl Transferase for Bioconjugation in Cell Lysate (pages 1958–1962)

      Chethana Kulkarni, Dr. Tamara L. Kinzer-Ursem and Prof. David A. Tirrell

      Version of Record online: 12 SEP 2013 | DOI: 10.1002/cbic.201300453

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      A site to behold: Robust site-specific functionalization of engineered proteins is achieved with N-myristoyl transferase (NMT) in bacterial cells. NMT tolerates non-natural substrate proteins as well as reactive fatty acid tags, rendering it a powerful tool for protein conjugation applications, including the construction of protein microarrays from lysate.

  7. Full Papers

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. Corrigendum
    5. News
    6. Highlights
    7. Communications
    8. Full Papers
    1. Unbiased Tracking of the Progression of mRNA and Protein Synthesis in Bulk and in Liposome-Confined Reactions (pages 1963–1966)

      Pauline van Nies, Zohreh Nourian, Maurits Kok, Roeland van Wijk, Jonne Moeskops, Ilja Westerlaken, Jos M. Poolman, Dr. Rienk Eelkema, Prof. Jan H. van Esch, Dr. Yutetsu Kuruma, Prof. Takuya Ueda and Dr. Christophe Danelon

      Version of Record online: 11 SEP 2013 | DOI: 10.1002/cbic.201300449

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      Colorful expression: The dynamics of gene expression in bulk solution and in liposome-confined reactions were analyzed with a two-reporter fluorescence assay by using the Spinach RNA aptamer and its fluorogenic probe for mRNA detection. In contrast to bulk expression, the levels of synthesized mRNA and protein inside lipid vesicles are heterogeneous and uncorrelated.

    2. Transfer RNA Misidentification Scrambles Sense Codon Recoding (pages 1967–1972)

      Dr. Radha Krishnakumar, Dr. Laure Prat, Dr. Hans-Rudolf Aerni, Dr. Jiqiang Ling, Prof. Dr. Chuck Merryman, Prof. John I. Glass, Prof. Jesse Rinehart and Prof. Dieter Söll

      Version of Record online: 2 SEP 2013 | DOI: 10.1002/cbic.201300444

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      Rewriting the code: A synthetic tRNA derived from a pyrrolysine (Pyl) tRNA contains an anticodon (CCG) of an arginine (Arg) tRNA. To recode Arg codons for Pyl, pyrrolysyl-tRNA synthetase (PylRS) must effectively compete for the synthetic tRNA with the endogenous arginyl-tRNA synthetase (ArgRS), which recognizes the anticodon CCG.

    3. You have full text access to this OnlineOpen article
      The Development of Selective Inhibitors of NagZ: Increased Susceptibility of Gram-Negative Bacteria to β-Lactams (pages 1973–1981)

      Dr. Keith A. Stubbs, Dr. John-Paul Bacik, G. Evan Perley-Robertson, Dr. Garrett E. Whitworth, Dr. Tracey M. Gloster, Dr. David J. Vocadlo and Dr. Brian L. Mark

      Version of Record online: 5 SEP 2013 | DOI: 10.1002/cbic.201300395

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      The development of selective and potent inhibitors of the β-glucosaminidase NagZ, which is an important enzyme in AmpC β-lactamase expression, based on the inhibitor 2-acetamido-2-deoxynojirimycin is described. In addition, the structure of a NagZ–inhibitor complex provides insight into the molecular basis for inhibition by these compounds.

    4. Effects of Charge and Charge Distribution on the Cellular Uptake of Multivalent Arginine-Containing Peptide–Polymer Conjugates (pages 1982–1990)

      Dr. Katharina Koschek, Dr. Margitta Dathe and Prof. Dr. Jörg Rademann

      Version of Record online: 24 SEP 2013 | DOI: 10.1002/cbic.201300365

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      Scrutinizing the door policy of living cells: Polymers loaded randomly with single arginine residues need to be more strongly charged than sequential arrangements for cell penetration, but are less toxic. Peptide–polymer compositions suitable for efficient cellular uptake and displaying negligible toxicity were determined at polymer concentrations relevant for intracellular functional studies.

    5. Rhabdopeptides as Insect-Specific Virulence Factors from Entomopathogenic Bacteria (pages 1991–1997)

      Daniela Reimer, Dr. Kimberly N. Cowles, Anna Proschak, Friederike I. Nollmann, Dr. Andrea J. Dowling, Marcel Kaiser, Prof. Dr. Richard ffrench- Constant, Prof. Dr. Heidi Goodrich-Blair and Prof. Dr. Helge B. Bode

      Version of Record online: 3 SEP 2013 | DOI: 10.1002/cbic.201300205

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      The insect does it: By using a promoter trap strategy for the detection of insect-inducible genes, highly N-methylated linear rhabdopeptides participating in virulence towards insects and their corresponding gene clusters have been identified in the entomopathogenic bacterium Xenorhabdus nematophila.

    6. A Unique Amino Transfer Mechanism for Constructing the β-Amino Fatty Acid Starter Unit in the Biosynthesis of the Macrolactam Antibiotic Cremimycin (pages 1998–2006)

      Keita Amagai, Ryoma Takaku, Prof. Dr. Fumitaka Kudo and Prof. Dr. Tadashi Eguchi

      Version of Record online: 6 SEP 2013 | DOI: 10.1002/cbic.201300370

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      Cluster ID: The cremimycin (cmi) biosynthetic gene cluster has been identified. A putative thioesterase homologue, CmiS1, catalyzes the Michael addition of glycine to non-2-enoic acid thioester, followed by hydrolysis to give N-carboxymethyl-3-aminononanoate, which is then oxidized by a putative FAD-dependent glycine oxidase homologue, CmiS2, to produce 3-aminonanoate.

    7. Versatile Substrates and Probes for IgA1 Protease Activity (pages 2007–2012)

      Santosh K. Choudary, Dr. Jiazhou Qiu, Prof. Dr. Andrew G. Plaut and Prof. Joshua A. Kritzer

      Version of Record online: 23 AUG 2013 | DOI: 10.1002/cbic.201300281

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      Cutting through the defenses: Diverse bacterial pathogens secrete immunoglobulin A1 (IgA1) proteases to assist in colonization, invasion, and immune evasion (see figure). Here we describe the first synthetic substrates and sensors for IgA1 proteases from diverse bacterial strains. These are applied to measuring IgA1 protease activity in buffer, in human cerebrospinal fluid, and in a high-throughput screen.

    8. The Antimicrobial Activity of Sub3 is Dependent on Membrane Binding and Cell-Penetrating Ability (pages 2013–2022)

      Inês M. Torcato, Dr. Yen-Hua Huang, Dr. Henri G. Franquelim, Dr. Diana D. Gaspar, Prof. David J. Craik, Prof. Miguel A. R. B. Castanho and Dr. Sónia Troeira Henriques

      Version of Record online: 26 AUG 2013 | DOI: 10.1002/cbic.201300274

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      Sub targets the enemy: By using AFM imaging, ζ potential, flow cytometry and fluorescence methodologies we show that the antimicrobial peptide Sub3 targets the bacterial membrane and internalises inside the cell at lethal concentrations without permeabilising the membranes. Furthermore, it internalises into human cells, yet is not toxic.

    9. Geranylation of Cyclic Dipeptides by the Dimethylallyl Transferase AnaPT Resulting in a Shift of Prenylation Position on the Indole Ring (pages 2023–2028)

      Daniel Pockrandt and Prof. Dr. Shu-Ming Li

      Version of Record online: 6 SEP 2013 | DOI: 10.1002/cbic.201300372

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      Preening the dipeptides: We investigated prenylation of six cyclic dipeptides by a dimethylallyl transferase of Neosartorya fischeri in the presence of geranyl diphosphate; the carbon chain length of the prenyl donor determines the prenylation position on the indole ring.

    10. Potential Rearrangements in the Reaction Catalyzed by the Indole Prenyltransferase FtmPT1 (pages 2029–2037)

      Niusha Mahmoodi and Prof. Martin E. Tanner

      Version of Record online: 6 SEP 2013 | DOI: 10.1002/cbic.201300385

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      Forward or reverse? The use of alternative substrates in the reaction catalyzed by the indole prenyltransferase FtmPT1 leads to novel alkaloids that are either reverse prenylated at C-3 or normal prenylated at N-1, C-3, or C-4. These results suggest that mechanisms involving C-3 prenylation followed by rearrangement could be responsible.

    11. The Multivalent Effect in Glycosidase Inhibition: Probing the Influence of Valency, Peripheral Ligand Structure, and Topology with Cyclodextrin-Based Iminosugar Click Clusters (pages 2038–2049)

      Dr. Camille Decroocq, Dr. Antoine Joosten, Raphaël Sergent, Teresa Mena Barragán, Prof. Carmen Ortiz Mellet and Prof. Philippe Compain

      Version of Record online: 6 SEP 2013 | DOI: 10.1002/cbic.201300283

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      Show me more: A first picture of the structural and thermodynamic parameters underlying strong multivalent effect in glycosidase inhibition has been achieved. This study combines isothermal titration calorimetry (ITC) experiments and structure–activity relationship investigation.

    12. Rescue of Functional CFTR Channels in Cystic Fibrosis: A Dramatic Multivalent Effect Using Iminosugar Cluster-Based Correctors (pages 2050–2058)

      Prof. Philippe Compain, Camille Decroocq, Dr. Antoine Joosten, Julien de Sousa, Dr. David Rodríguez-Lucena, Prof. Terry D. Butters, Dr. Johanna Bertrand, Dr. Romain Clément, Clément Boinot, Prof. Frédéric Becq and Dr. Caroline Norez

      Version of Record online: 13 SEP 2013 | DOI: 10.1002/cbic.201300312

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      Three is better than one: Iminosugar clusters displaying three copies of the clinical candidate miglustat lead to CFTR correctors that are superior by as much as two orders of magnitude. Trivalent iminosugars are up to 1000 times more potent than the corresponding monovalent models. These results provide the first description of a multivalent effect for correcting protein-folding defects in cells.

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