• Issue
    Volume 18, Issue 8
    694-823
    April 18, 2017

Cover Pictures

Free Access

Cover Picture: Modeling of S-Nitrosothiol–Thiol Reactions of Biological Significance: HNO Production by S-Thiolation Requires a Proton Shuttle and Stabilization of Polar Intermediates (ChemBioChem 8/2017)

  • Pages: 694
  • First Published: 29 March 2017
Description unavailable

The cover picture shows the main mechanistic steps toward the formation of nitroxyl, HNO—a potent bioactive molecule with a range of effects on the cardiovascular system—from S-nitrosothiols (RSNOs), which are ubiquitous biological derivatives of nitric oxide. RSNOs have long been suspected to be potential sources of endogenous HNO through S-thiolation reaction with thiols, although the overwhelming majority of reported RSNO–thiol reactions in vitro occur through an alternative trans-S-nitrosation pathway that does not yield HNO. In this issue, we show that the unusual antagonistic nature of RSNOs (shown as yin–yang in the picture) makes the S-thiolation reaction ripe for enzymatic catalysis, as the main steps of the reaction—proton transfer and formation of an unusual zwitterionic intermediate—can be effectively facilitated by the protein environment. We thank Caroline Kenwood and Carrie Hölzer (Milwaukee High School of the Arts) for their help with the graphic; the painting is by Caroline Kenwood. More information can be found in the full paper by Q. K. Timerghazin et al. on page 726 in Issue 8, 2017 (DOI: 10.1002/cbic.201600556).

Free Access

Inside Cover: Enantioselective Reduction of Citral Isomers in NCR Ene Reductase: Analysis of an Active-Site Mutant Library (ChemBioChem 8/2017)

  • Pages: 695
  • First Published: 29 March 2017
Description unavailable

The inside cover picture shows the ene reductase NCR as a “lemon press” converting either the (E)- or the (Z)-citral isomer to citronellal juice. Tryptophan residue 66 (marked in orange) or the alanine counterpart (red) at this position decides whether the juice contains (S)- or (R)-citronellal. The development of an R-selective citral reduction catalyst is of industrial importance for the synthesis of aroma chemicals such as (−)-menthol. The active-site-mutagenesis study presented in this paper reveals an important discrimination of the citral isomers by NCR ene reductase More information can be found in the communication by B. Hauer et al. on page 717 in Issue 8, 2017 (DOI: 10.1002/cbic.201700011).

Free Access

Back Cover: Lactosamine-Based Derivatives as Tools to Delineate the Biological Functions of Galectins: Application to Skin Tissue Repair (ChemBioChem 8/2017)

  • Pages: 824
  • First Published: 29 March 2017
Description unavailable

The back cover picture shows the collective keratinocyte migration that typically occurs during wound-healing. This highly efficient and complex process is driven by leader cells at the front of the cells, while the follower cells remain in close contact to move in concert. Galectin-3 is one of the key actors that control this fascinating example of cell–cell communication and multicellular organization. Blocking galectin-3 with small carbohydrate-based inhibitors, such as the one shown in blue, impairs the recruitment of actin (stained red by using rhodamine-coupled phalloidin) and results in the disorganization of actin fibers as well as that of podosomes, which are required for cell motility, and eventually leads to considerable delay in migration. More information can be found in the full paper by F. Poirier, C. Grandjean et al. on page 782 in Issue 8, 2017 (DOI: 10.1002/cbic.201600673).

Reviews

Nucleic-Acid-Templated Enzyme Cascades

  • Pages: 696-716
  • First Published: 02 February 2017
Description unavailable

To mimic cellular multienzyme complexes, enzymes have been attached to templates such as proteins and lipid bilayers in a manner suitable for cascade processes. DNA and RNA nanostructures were recently also shown to be promising templates for such processes. Here we highlight recent advances in nucleic-acid-templated substrate-transfer systems and discusses future perspectives.

Communications

Enantioselective Reduction of Citral Isomers in NCR Ene Reductase: Analysis of an Active-Site Mutant Library

  • Pages: 717-720
  • First Published: 08 February 2017
Description unavailable

Citral crossroad decisions: The W66A mutation acts as a lever for the formation of (R)-citronellal from (E/Z)-citral by NCR ene reductase. A very different stereoselectivity control is found for the E/Z isomers. This fundamental knowledge paves the way to inverted stereoselectivity by enzyme engineering.

A Novel Class of Natural FXR Modulators with a Unique Mode of Selective Co-regulator Assembly

  • Pages: 721-725
  • First Published: 10 February 2017
Description unavailable

Feroline and tschimgine are novel modulators that bind FXR with a two-pocket binding mode. They induce dynamic changes in the AF-2 surface, thereby leading to differential co-regulator profiling modulated by interactions unique to specific co-regulators. This finding provides a new pharmacophore for drug-design strategies for the regulation of FXR in the treatment of human diseases.

Full Papers

Modeling of S-Nitrosothiol–Thiol Reactions of Biological Significance: HNO Production by S-Thiolation Requires a Proton Shuttle and Stabilization of Polar Intermediates

  • Pages: 726-738
  • First Published: 07 February 2017
Description unavailable

Solving mechanistic mysteries: DFT modeling of nitroxyl (HNO) formation in S-thiolation reactions between thiols and S-nitrosothiols revealed three mechanistic phases and a polar intermediate. Stabilization of these intermediate species can serve as a possible catalytic mechanism of endogenous HNO production.

Characterisation of Photoaffinity-Based Chemical Probes by Fluorescence Imaging and Native-State Mass Spectrometry

  • Pages: 739-754
  • First Published: 08 February 2017
Description unavailable

Chemical probe structure–activity relationships: Chemical probes are small-molecule reagents used by researchers for labelling and detection of biomolecules. We demonstrate that a combination of in-gel fluorescence with native state mass spectrometry enables detailed characterisation of photoaffinity labelling (PAL) probe–protein interactions to establish probe structure–activity relationships.

Open Access

Development of an Efficient G-Quadruplex-Stabilised Thrombin-Binding Aptamer Containing a Three-Carbon Spacer Molecule

  • Pages: 755-763
  • First Published: 02 February 2017
Description unavailable

Give me some space! We investigated the impact of three different chemical modifications: a three-carbon spacer (spacer-C3), unlocked nucleic acid (UNA) and 3′-amino-modified UNA on the structural dynamics and stability of the thrombin-binding aptamer. The results showed that spacer-C3 introduction at the T7 loop position significantly improved stability and thrombin clotting time.

Insights from NMR Spectroscopy into the Conformational Properties of Man-9 and Its Recognition by Two HIV Binding Proteins

  • Pages: 764-771
  • First Published: 06 February 2017
Description unavailable

Sweet solutions. A robust method to produce uniform 13C,15N-labeled N-linked glycans facilitates the NMR spectroscopy of carbohydrates and 3 D structural studies of free glycans and those in complex with disease-relevant proteins.

Xanthomonas citri pv. citri Pathotypes: LPS Structure and Function as Microbe-Associated Molecular Patterns

  • Pages: 772-781
  • First Published: 10 February 2017
Description unavailable

Xanthomonas citri pv. citri, responsible for Asiatic citrus canker, is distinguished into three pathotypes that differ in host-range specificity. Characterization of the structures of the lipopolysaccharides from two pathotypes revealed an intriguing difference in LPS O-chain structure. Both lipopolysaccharides were tested for their ability to act as microbe-associated molecular patterns.

Lactosamine-Based Derivatives as Tools to Delineate the Biological Functions of Galectins: Application to Skin Tissue Repair

  • Pages: 782-789
  • First Published: 06 February 2017
Description unavailable

Galectin function tracking: Careful decoration of lactosamine core leads to potent and specific galectin-3 inhibitors that can be used to interfere with galectin-mediated signaling and to reveal their roles at the cellular level.

Slowly on, Slowly off: Bisubstrate-Analogue Conjugates of 5-Iodotubercidin and Histone H3 Peptide Targeting Protein Kinase Haspin

  • Pages: 790-798
  • First Published: 09 February 2017
Description unavailable

Bonding to haspin: Conjugates of 5-iodotubercidin and histone H3 peptide possess high affinity towards the mitotic protein kinase haspin. Our investigation revealed slow kinetics of association and dissociation, which reflects their unique mode of binding and consequently high selectivity.

Conjugate Vaccines from Bacterial Antigens by Squaric Acid Chemistry: A Closer Look

  • Pages: 799-815
  • First Published: 09 February 2017
Description unavailable

Fair and square: A new protocol for conjugating delipidated bacterial polysaccharides to proteins by using squarate chemistry shows a twofold increase in conjugation efficiency. The spent reagent can be regenerated, and the conjugate vaccine made from the conjugation reagent is comparable with the vaccine made from the parent antigen. CP: carrier protein; OSPc: O-SP–core.

Design and Discovery of New Combinations of Mutant DNA Polymerases and Modified DNA Substrates

  • Pages: 816-823
  • First Published: 03 February 2017
Description unavailable

Going forward: SFM19, a Taq polymerase variant, can synthesize 2′-modified DNA, but with limited product length. Through a combination of biochemical characterization and rational design, we designed novel mutant DNA polymerases capable of improved enzymatic modified-DNA synthesis.