Volume 8 Issue 8, August 2012

Volume 8 Issue 8

Phenylketonuria (PKU) is a metabolic disease characterized by increased phenylalanine in the blood and progressive mental retardation. Now, phenylalanine is shown to self-assemble into toxic amyloid fibrils at concentrations achieved in disease, and these fibrils accumulate in the brains of individuals with PKU and in mouse models of the disease. The image shows the elongated ordered phenylalanine assemblies stained with thioflavin T. Cover art by Erin Dewalt, based on an image from Lihi Adler-Abramovich. Article, p701


  • Editorial |

    We are changing the way we evaluate papers to ensure timely dissemination of chemical biology research.


  • Commentary |

    G protein–coupled receptors (GPCRs) are versatile molecular machines that regulate the majority of physiological responses to chemically diverse hormones and neurotransmitters. Recent breakthroughs in structural studies have advanced our understanding of GPCR signaling, particularly the selectivity of ligand recognition and receptor activation of G proteins.

    • Sébastien Granier
    •  & Brian Kobilka
  • Commentary |

    Defining G protein–coupled receptor ligand efficacy and biased agonism in precise chemical terms is one challenge posed by the current structural data that exists for this receptor family. Concepts classically used for understanding enzymes and other nonreceptor proteins may lead us in the right direction.

    • H Ongun Onaran
    •  & Tommaso Costa

Research Highlights

News and Views

  • News & Views |

    Siderophores are small molecules allowing microorganisms to competitively acquire iron from soils, aquatic systems or host proteins. New research shows that a siderophore secreted by some bacterial pathogens also binds copper and protects against host-derived copper toxicity during infection.

    • Amélie Garénaux
    •  & Charles M Dozois
  • News & Views |

    Bacterial pili are surface fibers that must resist high shearing forces to remain associated with their target. The Escherichia coli type 1 pilus chaperone FimC serves as a 'sensor', ensuring that only stable pilins become incorporated into the growing fiber.

    • David Neves
    •  & Andréa Dessen


  • Review Article |

    Dissecting the often subtle or time-sensitive roles of glycans in biology demands an increased availability of high-quality inhibitors for carbohydrate-processing enzymes. A review of lessons learned from other fields and considerations unique to glycobiology provides guidelines for development of these critical chemical tools.

    • Tracey M Gloster
    •  & David J Vocadlo

Brief Communications

  • Brief Communication |

    Elongation factor P is a conserved translational regulatory protein that has an unusual post-translational modification, in which Lys34 forms an amide linkage to (R)-β-lysine. Further characterization reveals that Lys34 is also hydroxylated, drawing parallels to a functional modification of eukaryotic initiation factor 5A.

    • Lauri Peil
    • , Agata L Starosta
    • , Kai Virumäe
    • , Gemma C Atkinson
    • , Tanel Tenson
    • , Jaanus Remme
    •  & Daniel N Wilson
  • Brief Communication |

    Bacterial resistance is propagated in part by metallo-β-lactamases, which hydrolyze and inactivate β-lactam antibiotics. An unusual cysteine residue in the active site is now shown to be critical for retaining the second metal ion, and thus enzyme activity, at low zinc concentrations.

    • Javier M González
    • , María-Rocío Meini
    • , Pablo E Tomatis
    • , Francisco J Medrano Martín
    • , Julia A Cricco
    •  & Alejandro J Vila


  • Article |

    Phenylketonuria (PKU) is characterized by increased levels of phenylalanine in the blood and progressive mental retardation. Now, phenylalanine is shown to form toxic amyloid fibrils at high concentrations, which accumulate in the brains of PKU patients and mouse models.

    • Lihi Adler-Abramovich
    • , Lilach Vaks
    • , Ohad Carny
    • , Dorit Trudler
    • , Andrea Magno
    • , Amedeo Caflisch
    • , Dan Frenkel
    •  & Ehud Gazit
  • Article |

    Hydrogen sulfide anion reacts with cellular electrophiles, including 8-nitro-cGMP, and sulfhydration products inhibit S-guanylation–dependent H-Ras activation in cardiac inflammatory injury models.

    • Motohiro Nishida
    • , Tomohiro Sawa
    • , Naoyuki Kitajima
    • , Katsuhiko Ono
    • , Hirofumi Inoue
    • , Hideshi Ihara
    • , Hozumi Motohashi
    • , Masayuki Yamamoto
    • , Makoto Suematsu
    • , Hitoshi Kurose
    • , Albert van der Vliet
    • , Bruce A Freeman
    • , Takahiro Shibata
    • , Koji Uchida
    • , Yoshito Kumagai
    •  & Takaaki Akaike
  • Article |

    Different key residues mediate melanocortin-4 receptor activation via the agonist αMSH or constitutive activation via interaction of the transmembrane domain with the N-terminal domain, and these modes are further distinguishable by the different effects of the physiological antagonist.

    • Baran A Ersoy
    • , Leonardo Pardo
    • , Sumei Zhang
    • , Darren A Thompson
    • , Glenn Millhauser
    • , Cedric Govaerts
    •  & Christian Vaisse
  • Article |

    Bacterial siderophores are known to bind various metals in vitro but are generally thought of as iron chelators in vivo. MS now demonstrates that yersiniabactin binds copper in vivo, with yersiniabactin expression correlated to bacterial fitness.

    • Kaveri S Chaturvedi
    • , Chia S Hung
    • , Jan R Crowley
    • , Ann E Stapleton
    •  & Jeffrey P Henderson