ChemBioChem

Cover image for Vol. 13 Issue 5

March 19, 2012

Volume 13, Issue 5

Pages 605–743

  1. Cover Picture

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Preview
    1. Cover Picture: NMR as an Effective Tool for the Structure Determination of Lasso Peptides (ChemBioChem 5/2012) (page 605)

      Dr. Xiulan Xie and Prof. Dr. Mohamed A. Marahiel

      Article first published online: 15 MAR 2012 | DOI: 10.1002/cbic.201290013

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      The cover picture shows a 3D structure and orthogonal views of capistruin, a highly stable lasso peptide produced by Burkholderia thailandensis. Lasso peptides are a class of ribosomally assembled natural products of bacterial origin. They feature a side-chain-to-backbone macrolactam ring through which eight or nine residues of the C-terminal part of the sequence are threaded. In the Minireview by M. A. Marahiel and X. Xie on p. 621 ff., the characteristic structural features of lasso peptides and the NMR spectroscopy methods used to define them are presented. The lasso structure was discovered 20 years ago, and nine structures have been published. Their compact fold makes lasso peptides highly stable against proteolytic degradation. This feature and their common biological activity as enzyme inhibitors suggest them to be interesting candidates for drug design. The cover picture was designed by Julian Hegemann (Philipps University Marburg).

  2. Inside Cover

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Preview
    1. Inside Cover: KlenTaq DNA Polymerase Adopts Unique Recognition States when Encountering Matched, Mismatched, and Abasic Template Sites: An NMR Study (ChemBioChem 5/2012) (page 606)

      Bastian Holzberger, M. Gabriele Pszolla, Prof. Dr. Andreas Marx and Dr. Heiko M. Möller

      Article first published online: 15 MAR 2012 | DOI: 10.1002/cbic.201290014

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      The inside cover picture shows the KlenTaq DNA polymerase in complex with DNA and a matching nucleoside triphosphate. H. M. Möller et al. (see article on p. 635 ff.) have identified unique recognition states of this enzyme by monitoring the NMR chemical-shift perturbations of 13C-labeled methionine methyl groups upon substrate binding. (The coordinates of the 3D structure were taken from PDB ID 3KTQ.)

  3. Graphical Abstract

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Preview
    1. Graphical Abstract: ChemBioChem 5/2012 (pages 607–613)

      Article first published online: 15 MAR 2012 | DOI: 10.1002/cbic.201290015

  4. News

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
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    1. Spotlights on our sister journals: ChemBioChem 5/2012 (pages 618–620)

      Article first published online: 15 MAR 2012 | DOI: 10.1002/cbic.201290016

  5. Minireview

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Preview
    1. NMR as an Effective Tool for the Structure Determination of Lasso Peptides (pages 621–625)

      Dr. Xiulan Xie and Prof. Dr. Mohamed A. Marahiel

      Article first published online: 25 JAN 2012 | DOI: 10.1002/cbic.201100754

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      Lasso peptides: unique structure and unusual stability: The highly ordered structures of lasso peptides comprising 16–21 amino acids render them unusually stable. The extremely neat 2D NMR spectra obtained in organic solvents makes NMR a powerful tool for determining these lasso structures.

  6. Highlight

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Preview
    1. Answers to the Carbon–Phosphorus Lyase Conundrum (pages 627–629)

      Dr. Qi Zhang and Prof. Dr. Wilfred A. van der Donk

      Article first published online: 14 FEB 2012 | DOI: 10.1002/cbic.201200020

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      Organophosphonates are widespread in nature, and their catabolic pathways are of great importance for many microorganisms. In a remarkable series of biochemical experiments, Raushel and co-workers reconstituted the carbon–phosphorus lyase activity, which cleaves the C[BOND]P bond of 5-phospho-α-D-ribosyl-methylphosphonate to produce methane and a cyclic phosphodiester in a reaction that requires S-adenosylmethionine and a [4Fe–4S] cluster.

  7. Communications

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
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    1. Chemical Maturation of a Bivalent Aptamer by Single Domain Variation (pages 631–634)

      Falk Rohrbach, Maha I. Fatthalla, Tina Kupper, Prof. Bernd Pötzsch, Dr. Jens Müller, Prof. Michael Petersen, Prof. Erik B. Pedersen and Prof. Günter Mayer

      Article first published online: 13 FEB 2012 | DOI: 10.1002/cbic.201200015

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      Two-pronged attack: We describe the maturation of a bivalent aptamer by a chemically driven two-step process. From an improved monovalent aptamer subdomain that had been modified by polycyclic aromatic hydrocarbons at individual positions, a mature bivalent variant with superior activities to its progenitor molecule was obtained through domain reassembly.

    2. KlenTaq DNA Polymerase Adopts Unique Recognition States when Encountering Matched, Mismatched, and Abasic Template Sites: An NMR Study (pages 635–639)

      Bastian Holzberger, M. Gabriele Pszolla, Prof. Dr. Andreas Marx and Dr. Heiko M. Möller

      Article first published online: 7 FEB 2012 | DOI: 10.1002/cbic.201100802

      Thumbnail image of graphical abstract

      On the tracks of a DNA polymerase: NMR provides insights into DNA synthesis in a virtually label-free manner and under close-to-physiological conditions. Through the monitoring of the chemical-shift changes of multiple 13C-methyl methionine residues we found unique recognition states for canonical and noncanonical cases, thus indicating enzymatic cycling through distinct paths.

    3. Psoromic Acid Derivatives: A New Family of Small-Molecule Pre-mRNA Splicing Inhibitors Discovered by a Stage-Specific High-Throughput in Vitro Splicing Assay (pages 640–644)

      Dr. Timur R. Samatov, Dr. Alexander Wolf, Dr. Peter Odenwälder, Dr. Sergey Bessonov, Dr. Céline Deraeve, Dr. Robin S. Bon, Prof. Dr. Herbert Waldmann and Prof. Dr. Reinhard Lührmann

      Article first published online: 14 FEB 2012 | DOI: 10.1002/cbic.201100790

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      Snapshots of spliceosome assembly: A high-throughput in vitro splicing assay has been developed for screening a compound library. The discovered family of pre-mRNA splicing inhibitors comprises lichen secondary metabolites that allow the enrichment of the spliceosomal complexes formed after the spliceosome activation step. Here we identify the structural features important for the compounds' inhibitory activity.

    4. Esterases with an Introduced Amidase-Like Hydrogen Bond in the Transition State Have Increased Amidase Specificity (pages 645–648)

      Dr. Per-Olof Syrén, Peter Hendil-Forssell, Lucie Aumailley, Dr. Werner Besenmatter, Farida Gounine, Allan Svendsen, Dr. Mats Martinelle and Prof. Karl Hult

      Article first published online: 29 FEB 2012 | DOI: 10.1002/cbic.201100779

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      By using rational design an amidase-like hydrogen bond (indicated by the arrow) was introduced into the transition states of Candida antarctica lipase B and Humicola insolens cutinase. The best mutant displayed a 50-fold increase in amide over ester bond hydrolysis compared to the wild type.

    5. Directed Evolution of Highly Selective Proteases by Using a Novel FACS-Based Screen that Capitalizes on the p53 Regulator MDM2 (pages 649–653)

      Prof. Tae Hyeon Yoo, Mark Pogson, Prof. Brent L. Iverson and Prof. George Georgiou

      Article first published online: 14 FEB 2012 | DOI: 10.1002/cbic.201100718

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      We describe a novel method for the isolation of selective protease variants displayed on the surface of E. coli. The method relies on the electrostatic capture of an autoinhibited protein on the cell surface, combined with external labeling using a fluorophore-conjugated binding peptide (PMI-FL). Using this method, we isolated an OmpT variant that hydrolyzes a target sequence (between Ala-Arg) with high selectivity.

    6. Covalent Tagging of Phosphorylated Peptides by Phosphate-Specific Deoxyribozymes (pages 654–657)

      Dr. Amit Sachdeva, Dr. Madhavaiah Chandra, Jagadeeswaran Chandrasekar and Prof. Scott K. Silverman

      Article first published online: 7 FEB 2012 | DOI: 10.1002/cbic.201200048

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      Hold your P's: Phosphorylated tyrosine and serine residues in peptides have been modified selectively by DNA catalysts (see graphic). These deoxyribozymes catalyze covalent attachment of an RNA tag to a range of peptide sequences, thus a proof of principle for a new approach to phosphopeptide analysis is established.

    7. A Fresh Look at Adenosine-Binding DNA Motifs (pages 658–660)

      Mihaela Barbu and Prof. Dr. Milan N. Stojanovic

      Article first published online: 28 FEB 2012 | DOI: 10.1002/cbic.201200024

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      One is enough: For many years an adenosine binding aptamer with two binding sites has been used in DNA devices. We now show that an aptamer with a single binding site may also be used.

    8. Cyclodextrin-Based Iminosugar Click Clusters: The First Examples of Multivalent Pharmacological Chaperones for the Treatment of Lysosomal Storage Disorders (pages 661–664)

      Camille Decroocq, Dr. David Rodríguez-Lucena, Dr. Kyoko Ikeda, Prof. Naoki Asano and Prof. Philippe Compain

      Article first published online: 16 FEB 2012 | DOI: 10.1002/cbic.201200005

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      Seven-arm chaperone: A modest μM inhibitor of glucosylceramide β-glucosidase (GCase) has been transformed into a potent low-nM inhibitor by multivalency. This iminosugar inhibitor acts as a pharmacological chaperone and increases residual GCase activity in fibroblasts from Gaucher patients. These results open the way to a new class of chaperones for the treatment of lysosomal diseases.

  8. Full Papers

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Preview
    1. Detection of Early Abl Kinase Activation after Ionizing Radiation by Using a Peptide Biosensor (pages 665–673)

      Dr. Jiabin Tang, Prof. Jean Y. Wang and Prof. Laurie L. Parker

      Article first published online: 14 FEB 2012 | DOI: 10.1002/cbic.201100763

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      Damage limitation: A peptide biosensor for intracellular Abl kinase activation helps elucidate a potential, early, ATM- and DNAPK-dependent role for Abl in the response to DNA damage from ionizing radiation. The substrate peptide is combined with a binding sequence and a cell-permeability tag to enable uptake and specific phosphorylation by overexpressed Abl kinase in the cell.

    2. Flexible and General Synthesis of Functionalized Phosphoisoprenoids for the Study of Prenylation in vivo and in vitro (pages 674–683)

      Dr. Debapratim Das, Zakir Tnimov, Dr. Uyen T. T. Nguyen, Dr. Govindaraju Thimmaiah, Dr. Harriet Lo, Dr. Daniel Abankwa, Dr. Yaowen Wu, Prof. Dr. Roger S. Goody, Prof. Dr. Herbert Waldmann and Prof. Dr. Kirill Alexandrov

      Article first published online: 20 FEB 2012 | DOI: 10.1002/cbic.201100733

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      Prenylation probes: Eukaryotic protein prenyltransferases modify polypeptides with isoprenoid lipids. Modification of isoprenoids with reporter groups allows the creation of probes for the analysis of protein prenylation in vitro and in vivo. An amine-derivatized isoprenoid scaffold was used as a novel starting point for the synthesis of functionalized phosphoisoprenoid libraries.

    3. Effect of N3 Modifications on the Affinity of Spin Label ç for Abasic Sites in Duplex DNA (pages 684–690)

      Sandip A. Shelke and Prof. Dr. Snorri Th. Sigurdsson

      Article first published online: 8 MAR 2012 | DOI: 10.1002/cbic.201100728

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      Spin-label ligands: N3 derivatives of the spin label ç were synthesized and used for noncovalent site-directed spin labeling of duplex DNAs containing abasic sites. EPR spectra showed that derivatives containing basic functional groups had higher binding affinity and solubility. These are promising candidates for distance measurement in nucleic acids by pulsed EPR spectroscopy.

    4. Directed Evolution of Subtilisin E into a Highly Active and Guanidinium Chloride- and Sodium Dodecylsulfate-Tolerant Protease (pages 691–699)

      Zhenwei Li, Prof. Dr. Danilo Roccatano, Prof. Dr. Michael Lorenz and Prof. Dr. Ulrich Schwaneberg

      Article first published online: 8 MAR 2012 | DOI: 10.1002/cbic.201100714

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      Evolving tolerance: Amino acid substitutions in wild-type subtilisin E were identified to improve GdmCl and SDS resistance by using the colorimetric substrate Suc-Ala-Ala-Pro-Phe-pNA. The four substitutions (S62, A153, G166, I205; yellow) were identified by directed evolution. The catalytic triad (Asp32, His64 and Ser221) is shown in blue, and substrate Suc-AAPF-pNA is shown in red.

    5. Synthesis of C8-Arylamine-Modified 2′-Deoxyadenosine Phosphoramidites and their Site-Specific Incorporation into Oligonucleotides (pages 700–712)

      Dr. Zita Szombati, Sabrina Baerns, Prof. Dr. Andreas Marx and Prof. Dr. Chris Meier

      Article first published online: 29 FEB 2012 | DOI: 10.1002/cbic.201100573

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      C8-NAc-arylamine adducts of 2′-deoxyadenosine with various aromatic amines were synthesised by cross-coupling chemistry and then converted into their 3′-phosphoramidites. These building blocks were used in DNA syntheses to produce site-specifically damaged NarI-, EcoRI- and 20-mer oligonucleotides. The oligonucleotides were used in studies of biophysical properties and restriction endonucleases, as well as DNA polymerase assays.

    6. Chemical Rescue of Active Site Mutants of S. pneumoniae Surface Endonuclease EndA and Other Nucleases of the HNH Family by Imidazole (pages 713–721)

      Dr. Marika Midon, Dr. Oleg Gimadutdinow, Dr. Gregor Meiss, Prof. Dr. Peter Friedhoff and Prof. Dr. Alfred Pingoud

      Article first published online: 17 FEB 2012 | DOI: 10.1002/cbic.201100775

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      Nuclease activation: The HNH motif characterizes many nucleases, among them EndA from Streptococcus pneumoniae. One of the His residues is responsible for activating a water molecule for phosphodiester bond cleavage. Its replacement by other amino acids leads to inactive enzymes. However, subsequent addition of imidazole can rescue catalytic activity in vitro and in vivo.

    7. Identification of the First Known Inhibitors of O-Acetylpeptidoglycan Esterase: A Potential New Antibacterial Target (pages 722–731)

      John M. Pfeffer and Prof. Anthony J. Clarke

      Article first published online: 20 FEB 2012 | DOI: 10.1002/cbic.201100744

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      A high-throughput screen was developed to identify the first inhibitors of O-acetylpeptidoglycan esterase, the enzyme responsible for the removal of the O-acetyl groups of the peptidoglycan of many pathogenic bacteria. Seven compounds differing in structure were found and further analysis validated the enzyme as a potential new antibacterial target.

    8. Selective Isotopic Unlabeling of Proteins Using Metabolic Precursors: Application to NMR Assignment of Intrinsically Disordered Proteins (pages 732–739)

      Dr. Rodolfo M. Rasia, Dr. Bernhard Brutscher and Dr. Michael J. Plevin

      Article first published online: 8 MAR 2012 | DOI: 10.1002/cbic.201100678

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      Stop the scramble! In NMR spectroscopic studies of recombinant proteins selective isotopic unlabeling can be used to obtain residue-type information and reduce spectral overlap. However, scrambling of unlabeled atoms by bacterial metabolic pathways can greatly complicate NMR spectra. Here nitrogen-free metabolic precursors are shown to provide robust, predictable and residue-type-selective unlabeling of otherwise uniformly isotope-labeled proteins.

  9. Preview

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Preview
    1. You have free access to this content
      Preview: ChemBioChem 6/2012 (page 743)

      Article first published online: 15 MAR 2012 | DOI: 10.1002/cbic.201290017

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