ChemBioChem

Cover image for Vol. 10 Issue 18

December 14, 2009

Volume 10, Issue 18

Pages 2809–2951

  1. Cover Picture

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Minireview
    8. Highlights
    9. Communications
    10. Full Papers
    11. Book Review
    12. Preview
    1. Cover Picture: Increased Enantioselectivity by Engineering Bottleneck Mutants in an Esterase from Pseudomonas fluorescens (ChemBioChem 18/2009) (page 2809)

      Anna Schließmann, Aurelio Hidalgo, José Berenguer and Uwe T. Bornscheuer

      Version of Record online: 4 DEC 2009 | DOI: 10.1002/cbic.200990082

      Thumbnail image of graphical abstract

      The cover picture shows (R)-1-phenyl-2-propyl acetate docked in the active site of a quadruple mutant (mutant Q) of the Pseudomonas fluorescens esterase I. The four point mutations involved the replacement of four Phe with Leu residues in the area lining the entrance to the active site, which was termed the bottleneck (in blue). Substitutions in this area cause changes in enantioselectivity, both due to direct interaction with the substrate and to restriction of substrate access to the active site. The detail shows the catalytic residues in green, and the bottleneck residues of the wild-type (in dark red) and of mutant Q (in dark blue) interacting in a clearly different way with (R)-1-phenyl-2-propyl acetate (light red and light blue for the interaction with the wild-type enzyme and mutant Q, respectively). More information can be found on p. 2920 ff, U. Bornscheuer et al. Cover art by J. Belio.

  2. Inside Cover

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Minireview
    8. Highlights
    9. Communications
    10. Full Papers
    11. Book Review
    12. Preview
    1. Inside Cover: Leveraging a Small-Molecule Modification to Enable the Photoactivation of Rho GTPases (ChemBioChem 18/2009) (page 2810)

      Katryn R. Harwood and Stephen C. Miller

      Version of Record online: 4 DEC 2009 | DOI: 10.1002/cbic.200990083

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      The inside cover picture shows the Rho GTPase Cdc42 modified with a photolabile small molecule that recruits the protein HaloTag. This two-part modification system prevents Cdc42 from binding and being activated by nucleotide. Irradiation with longwave UV light releases the HaloTag-bound photoligand and restores the GTP-dependent activity of Cdc42 as demonstrated in the paper by K. R. Harwood and S. C. Miller on p. 2855 ff.

  3. Graphical Abstract

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Minireview
    8. Highlights
    9. Communications
    10. Full Papers
    11. Book Review
    12. Preview
  4. News

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Minireview
    8. Highlights
    9. Communications
    10. Full Papers
    11. Book Review
    12. Preview
  5. Review

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Minireview
    8. Highlights
    9. Communications
    10. Full Papers
    11. Book Review
    12. Preview
    1. Engineering Allosteric Regulation into Biological Catalysts (pages 2824–2835)

      Jacques Fastrez

      Version of Record online: 24 NOV 2009 | DOI: 10.1002/cbic.200900590

      Thumbnail image of graphical abstract

      'Allo 'Allo! Enzymes or ribozymes have been engineered to incorporate allosteric sites that bind ligands unrelated to their substrates. Random mutagenesis of surface residues followed by selection or appendage of ligand-binding modules to biocatalysts affords enzymes or ribozymes with activity that can be regulated by allosteric ligand binding.

  6. Minireview

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Minireview
    8. Highlights
    9. Communications
    10. Full Papers
    11. Book Review
    12. Preview
    1. Copper and Zinc Binding to Amyloid-β: Coordination, Dynamics, Aggregation, Reactivity and Metal-Ion Transfer (pages 2837–2845)

      Peter Faller

      Version of Record online: 28 OCT 2009 | DOI: 10.1002/cbic.200900321

      Thumbnail image of graphical abstract

      The metal side of Alzheimer's disease: Cu and Zn ions have been shown to be involved in two key steps of Alzheimer's disease (AD): aggregation of the peptide amyloid-β (Aβ) and production of reactive oxygen species. Cu/Zn–Aβ complexes are observed in AD, but not under healthy conditions. Thus, the understanding of how these metal ions interact with Aβ has become an important issue for AD.

  7. Highlights

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Minireview
    8. Highlights
    9. Communications
    10. Full Papers
    11. Book Review
    12. Preview
    1. New Ways of Killing the Beast: Prospects for Inorganic–Organic Hybrid Nanomaterials as Antibacterial Agents (pages 2847–2850)

      Julia E. Bandow and Nils Metzler-Nolte

      Version of Record online: 10 NOV 2009 | DOI: 10.1002/cbic.200900628

      Thumbnail image of graphical abstract

      Joining forces: New approaches for antibiotic therapy use inorganic nanoparticles loaded with porphyrin photosensitizers. When irradiated with visible light, these nanoparticles produce singlet oxygen, which in turn kills nearby bacteria. Recent studies identify necessary modifications of the nanoparticles for good adherence to the bacterial membrane and explore the potential of this strategy for combating multiresistant bacterial strains.

    2. Protein Biosynthesis on Ribosomes in Molecular Resolution: Nobel Prize for Chemistry 2009 Goes to Three Chemical Biologists (pages 2851–2853)

      Mathias Sprinzl and Volker A. Erdmann

      Version of Record online: 24 NOV 2009 | DOI: 10.1002/cbic.200900652

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      Nobel 2009. Ada Yonath, Thomas A. Steitz and Venkatraman Ramakrishnan have shared the 2009 Nobel Prize for Chemistry for their contributions to solving the three-dimensional structure of bacterial ribosomes by employing X-ray crystallography. A detailed view of this complex machinery will help to develop new synthetic antibiotics.

  8. Communications

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Minireview
    8. Highlights
    9. Communications
    10. Full Papers
    11. Book Review
    12. Preview
    1. Leveraging a Small-Molecule Modification to Enable the Photoactivation of Rho GTPases (pages 2855–2857)

      Katryn R. Harwood and Stephen C. Miller

      Version of Record online: 28 OCT 2009 | DOI: 10.1002/cbic.200900546

      Thumbnail image of graphical abstract

      Protein photocontrol: Covalent modification of the nucleotide-binding pocket of the Rho GTPase Cdc42 with photolabile small molecules fails to prevent activation by GTP (1). To allow the construction of a photoactivatable Cdc42, we developed a new strategy that leverages a small-molecule photocage into a very large protein modification. This protein fusion product could be easily purified and could no longer be activated by GTP (2). Irradiation with long-wave UV light restores GTP-dependent activity (3).

    2. Synthesis of Threefold Glycosylated Proteins using Click Chemistry and Genetically Encoded Unnatural Amino Acids (pages 2858–2861)

      Emine Kaya, Katrin Gutsmiedl, Milan Vrabel, Markus Müller, Peter Thumbs and Thomas Carell

      Version of Record online: 6 NOV 2009 | DOI: 10.1002/cbic.200900625

      Thumbnail image of graphical abstract

      Click to convert. Three encoded alkyne and alkene amino acids were incorporated into yellow fluorescent protein (YFP) and subsequently glycosylated by using the CuI catalyzed click reaction, as illustrated in the scheme.

    3. Covalent-Bond-Based Immobilization Approaches for Single-Molecule Fluorescence (pages 2862–2866)

      Elvin A. Alemán, Heidi S. Pedini and David Rueda

      Version of Record online: 12 NOV 2009 | DOI: 10.1002/cbic.200900640

      Thumbnail image of graphical abstract

      Two new approaches, click-chemistry and disulfide bond bridges, to surface-immobilizing nucleic acids for single-molecule fluorescence experiments using covalent bonds and self-assembled monolayers are reported. Both approaches are specific and yield comparable results to the avidin–biotin linkage, but offer new surface-chemical properties that might be advantageous to prevent nonspecific binding of biopolymers to the surface and to expand the range of fluorescent probes that can be employed in single-molecule studies.

    4. Effects of Fluorination on the Folding Kinetics of a Heterodimeric Coiled Coil (pages 2867–2870)

      Mario Salwiczek and Beate Koksch

      Version of Record online: 26 OCT 2009 | DOI: 10.1002/cbic.200900518

      Thumbnail image of graphical abstract

      The fast and the fluorous: SPR is a powerful method to investigate fast interactions between peptides and proteins. Differences of even one fluorine atom within a side chain can be detected. It is shown that fluorination of a single residue within the hydrophobic core results in a twofold increase in the association rate of a coiled-coil heterodimer. The observations furthermore reinvigorate the question whether fluorine–fluorine contacts in the unfolded state affect the kinetics of folding.

    5. Elucidating Protein Binding Mechanisms by Variable-c ITC (pages 2871–2873)

      Lee A. Freiburger, Karine Auclair and Anthony K. Mittermaier

      Version of Record online: 23 OCT 2009 | DOI: 10.1002/cbic.200900614

      Thumbnail image of graphical abstract

      Isothermal titration calorimetry (ITC) has great potential for studying allosteric and cooperative interactions. However, a single set of ITC data can be compatible with several different binding models; this leaves the actual binding mechanism uncertain. Here we report a simple approach for resolving this ambiguity, based on a global analysis of variable-c value ITC datasets obtained with a range of sample concentrations.

  9. Full Papers

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Minireview
    8. Highlights
    9. Communications
    10. Full Papers
    11. Book Review
    12. Preview
    1. Computational Study of the Lipase-Mediated Desymmetrisation of 2-Substituted-Propane-1,3-Diamines (pages 2875–2883)

      Eduardo García-Urdiales, Eduardo Busto, Nicolás Ríos-Lombardía, Vicente Gotor-Fernández and Vicente Gotor

      Version of Record online: 2 NOV 2009 | DOI: 10.1002/cbic.200900412

      Thumbnail image of graphical abstract

      The shorter the better! The introduction of a methylene group as linker between the aryl ring and the 2-carbon of prochiral propane-1,3-diamines decreases the enantioselectivity of the Pseudomonas cepacia lipase-catalysed alkoxycarbonylation by approximately 30 %. As illustrated here, the unfavourable intramolecular interactions (spheres) of the slow-reacting orientation (black) vanish in the presence of the methylene group (grey).

    2. Interactions of KLA Amphipathic Model Peptides with Lipid Monolayers (pages 2884–2892)

      Andreas Erbe, Andreas Kerth, Margitta Dathe and Alfred Blume

      Version of Record online: 28 OCT 2009 | DOI: 10.1002/cbic.200900444

      Thumbnail image of graphical abstract

      Under pressure: Amphipathic model peptides of the KLAL family incorporate into anionic lipid monolayers in an α-helical conformation at high surface pressures. At lower surface pressures, α-helical peptides bound to the lipids and β-sheets bound to the free water surface coexist.

    3. Synthesis, Conjugation, and Immunological Evaluation of the Serogroup 6 Pneumococcal Oligosaccharides (pages 2893–2899)

      Archana R. Parameswar, In Ho Park, Rina Saksena, Pavol Kováč, Moon H. Nahm and Alexei V. Demchenko

      Version of Record online: 23 OCT 2009 | DOI: 10.1002/cbic.200900587

      Thumbnail image of graphical abstract

      Being square pays off: The first synthesis of the newly discovered oligosaccharide of pneumococcal serotype 6C and its spacer-containing analogue is reported. Conjugation of the spacer-containing oligosaccharides of pneumococcal saccharides with a BSA protein carrier was carried out by using a squaric-acid approach. The conjugates tested with a rabbit antiserum pool showed that the synthetic carbohydrate conjugates express epitopes found in native capsular polysaccharides.

    4. Chivosazoles A and F, Cytostatic Macrolides from Myxobacteria, Interfere with Actin (pages 2900–2903)

      Randi Diestel, Herbert Irschik, Rolf Jansen, Mohammed W. Khalil , Hans Reichenbach and Florenz Sasse

      Version of Record online: 22 OCT 2009 | DOI: 10.1002/cbic.200900562

      Thumbnail image of graphical abstract

      Acting on actin: Chivosazoles A and F induce a breakdown of the actin cytoskeleton of mammalian cells. Their mode of action differs from other microfilament disrupting drugs such as rhizopodin and cytochalasin D.

    5. A Conserved Lysine in β-Lactam Synthetase Assists Ring Cyclization: Implications for Clavam and Carbapenem Biosynthesis (pages 2904–2912)

      Mary L. Raber, Alvaro Castillo, Alexander Greer and Craig A. Townsend

      Version of Record online: 30 OCT 2009 | DOI: 10.1002/cbic.200900389

      Thumbnail image of graphical abstract

      Strained ring formation made easy: Ring strain in the β-lactam antibiotics is central to their biological activity. A conserved lysyl residue is shown to stabilize the transition states for enzymic cyclization of adenylated β-amino acid precursors (as illustrated in the scheme) to clavulanic acid and the carbapenems—two of the four known families of β-lactam antibiotics.

    6. Molecular Mechanism of the Hydration of Candida antarctica Lipase B in the Gas Phase: Water Adsorption Isotherms and Molecular Dynamics Simulations (pages 2913–2919)

      Ricardo J. F. Branco, Marianne Graber, Vinciane Denis and Jürgen Pleiss

      Version of Record online: 21 OCT 2009 | DOI: 10.1002/cbic.200900544

      Thumbnail image of graphical abstract

      It's in the water: The hydration of Candida antarctica lipase B (CALB) in the gas phase was investigated at different water acitivities (aw) by measuring water sorption isotherms and by molecular modeling. At low water activities (aw<0.5) water binds to specific sites at the protein surface. At high water activities, a spanning water network gradually forms covering the hydrophilic surface of CALB, with the exception of the hydrophobic substrate-binding site (green).

    7. Increased Enantioselectivity by Engineering Bottleneck Mutants in an Esterase from Pseudomonas fluorescens (pages 2920–2923)

      Anna Schließmann, Aurelio Hidalgo, José Berenguer and Uwe T. Bornscheuer

      Version of Record online: 21 OCT 2009 | DOI: 10.1002/cbic.200900563

      Thumbnail image of graphical abstract

      Hitting the bottleneck: Four bulky and hydrophobic amino acid residues forming a bottleneck to the entrance of the active site of the Pseudomonas fluorescens esterase I were mutated. This yielded variants that not only had better substrate access to the active site, but also increased enantioselectivity.

    8. Diarylpropane-1,3-dione Derivatives as TetR-Inducing Tetracycline Mimetics: Synthesis and Biological Investigations (pages 2924–2933)

      Christian Kormann, Irina Pimenta, Stefan Löber, Cornelius Wimmer, Harald Lanig, Timothy Clark, Wolfgang Hillen and Peter Gmeiner

      Version of Record online: 2 NOV 2009 | DOI: 10.1002/cbic.200900564

      Thumbnail image of graphical abstract

      Cutting down on the essential: The β-diketone structure of tetracycline is known to chelate MgII to form a metal complex, which has been proven to be the TetR inducing agent. We designed novel, de novo TetR binders on 1,3-diaryl substituted β-diketones that retain this key structural motif. The introduction of additional tetracycline functional groups of gave insights into the structure–activity relationships of TetR induction and antibiotic potency.

    9. A Minimalist Substrate for Enzymatic Peptide and Protein Conjugation (pages 2934–2943)

      James W. Wollack, Julie M. Silverman, Christopher J. Petzold, Joseph D. Mougous and Mark D. Distefano

      Version of Record online: 23 OCT 2009 | DOI: 10.1002/cbic.200900566

      Thumbnail image of graphical abstract

      On the box: Labeling proteins with alkyne/azide functionalized tags allows for subsequent [3+2] Huisgen cycloaddition with other azide/alkyne containing molecules. We report the synthesis of a short alkyne-containing molecule (C5-alkyne) that proved to be a substrate for protein farnesyltransferase. Proteins modified with this substrate had improved solubility compared with those modified with longer azide-containing substrates. Also, the last three amino acids of “CAAX box” proteins labeled with C5-alkyne can be selectively removed with a peptidase.

  10. Book Review

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Minireview
    8. Highlights
    9. Communications
    10. Full Papers
    11. Book Review
    12. Preview
  11. Preview

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Minireview
    8. Highlights
    9. Communications
    10. Full Papers
    11. Book Review
    12. Preview
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      Preview: ChemBioChem 1/2010 (page 2951)

      Version of Record online: 4 DEC 2009 | DOI: 10.1002/cbic.200990086

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