Volume 8 Issue 12, December 2012

Volume 8 Issue 12

Crystal structures and activity assays with modified substrates provide new insights into O-GlcNAc transferase’s elusive reaction coordinate. This cartoon shows a rendition of OGT’s reaction trajectory in an overlay of the protein with ternary substrates and ternary products. Cover art by Erin Dewalt, based on imagery from Michael Lazarus. Brief Communication, p966; Article, p969; News & Views, p952

Editorials

  • Editorial |

    The launch of the International Chemical Biology Society represents an important step for chemical biology.

  • Editorial |

    The Methods section of original research papers will be published online only starting in 2013.

Research Highlights

News and Views

  • News & Views |

    Post-translational modification of proteins by N-acetylglucosamine (O-GlcNAc) is carried out by a single glycosyltransferase, OGT. Two independent groups have generated structures of ternary complexes that elegantly illuminate substrate and product binding modes, and thus the overall reaction coordinate, but the respective authors differ in their choice of catalytic base.

    • Stephen G Withers
    •  & Gideon J Davies
  • News & Views |

    A major determinant of the ion flux rate through acetylcholine receptors is a ring of five residues, four glutamates and a glutamine, at the channel's cytoplasmic mouth. The glutamates adopt alternate rotamer conformations so that only two directly affect channel conductance.

    • Myles H Akabas
  • News & Views |

    Combinatorial protein engineering based on structural data and the differential expression of alternate second receptor chains for interleukin-4 (IL-4) is used to modify and tune cellular specificity on primary human cells.

    • Shane Miersch
    •  & Sachdev S Sidhu

Brief Communications

  • Brief Communication |

    TsrM, a member of the radical SAM enzyme family, is shown to catalyze tryptophan methylation en route to thiostrepton A with the help of a methylcobalamin cofactor and without generating the canonical 5-deoxyadenosyl radical.

    • Stéphane Pierre
    • , Alain Guillot
    • , Alhosna Benjdia
    • , Corine Sandström
    • , Philippe Langella
    •  & Olivier Berteau
  • Brief Communication |

    The identification of Escherichia coli ycfD and human MINA53 and NO66 as ribosomal amino acid hydroxylases defines a role for 2-oxoglutarate/iron-dependent oxygenases in translational regulation.

    • Wei Ge
    • , Alexander Wolf
    • , Tianshu Feng
    • , Chia-hua Ho
    • , Rok Sekirnik
    • , Adam Zayer
    • , Nicolas Granatino
    • , Matthew E Cockman
    • , Christoph Loenarz
    • , Nikita D Loik
    • , Adam P Hardy
    • , Timothy D W Claridge
    • , Refaat B Hamed
    • , Rasheduzzaman Chowdhury
    • , Lingzhi Gong
    • , Carol V Robinson
    • , David C Trudgian
    • , Miao Jiang
    • , Mukram M Mackeen
    • , James S Mccullagh
    • , Yuliya Gordiyenko
    • , Armin Thalhammer
    • , Atsushi Yamamoto
    • , Ming Yang
    • , Phebee Liu-Yi
    • , Zhihong Zhang
    • , Marion Schmidt-Zachmann
    • , Benedikt M Kessler
    • , Peter J Ratcliffe
    • , Gail M Preston
    • , Mathew L Coleman
    •  & Christopher J Schofield
  • Brief Communication |

    Riboswitches—RNA motifs that regulate gene expression in response to binding of specific ligands—have been identified for many small-molecule metabolites. An ATP-binding element in the ydaO mRNA of Bacillus subtilis provides the first example of an ATP-responsive riboswitch.

    • Peter Y Watson
    •  & Martha J Fedor
  • Brief Communication |

    Understanding the reaction mechanism of OGT, responsible for O-GlcNAcylating various protein substrates, has been hampered by a lack of structural information. Snapshots of ternary complexes along the reaction coordinate now provide evidence for substrate participation in an electrophilic migration mechanism.

    • Michael B Lazarus
    • , Jiaoyang Jiang
    • , Tracey M Gloster
    • , Wesley F Zandberg
    • , Garrett E Whitworth
    • , David J Vocadlo
    •  & Suzanne Walker

Articles

  • Article |

    OGT modifies numerous proteins with O-GlcNAc, but the mechanism for this reaction has been difficult to define. Ternary crystal structures and activity assays with substrate analogs now provide evidence that the α-phosphate of the donor substrate is the catalytic base.

    • Marianne Schimpl
    • , Xiaowei Zheng
    • , Vladimir S Borodkin
    • , David E Blair
    • , Andrew T Ferenbach
    • , Alexander W Schüttelkopf
    • , Iva Navratilova
    • , Tonia Aristotelous
    • , Osama Albarbarawi
    • , David A Robinson
    • , Megan A Macnaughtan
    •  & Daan M F van Aalten
  • Article |

    A kinase inhibitor based on a known type II inhibitor allosterically inhibits the RNase activity of IRE1α in vitro and in cells via the ATP-binding site in the kinase domain.

    • Likun Wang
    • , B Gayani K Perera
    • , Sanjay B Hari
    • , Barun Bhhatarai
    • , Bradley J Backes
    • , Markus A Seeliger
    • , Stephan C Schürer
    • , Scott A Oakes
    • , Feroz R Papa
    •  & Dustin J Maly
  • Article |

    The creation and application of engineered constructs specific for one of two IL-4 coreceptors explain how immune signaling is limited by coreceptor concentration and establish specific roles for type II receptor–specific signaling in dendritic cell differentiation.

    • Ilkka S Junttila
    • , Remi J Creusot
    • , Ignacio Moraga
    • , Darren L Bates
    • , Michael T Wong
    • , Michael N Alonso
    • , Megan M Suhoski
    • , Patrick Lupardus
    • , Martin Meier-Schellersheim
    • , Edgar G Engleman
    • , Paul J Utz
    • , C Garrison Fathman
    • , William E Paul
    •  & K Christopher Garcia

Corrigendum

Errata

  • Erratum |

    • Dimitrios Anastasiou
    • , Yimin Yu
    • , William J Israelsen
    • , Jian-kang Jiang
    • , Matthew B Boxer
    • , Bum Soo Hong
    • , Wolfram Tempel
    • , Svetoslav Dimov
    • , Min Shen
    • , Abhishek Jha
    • , Hua Yang
    • , Katherine R Mattaini
    • , Christian M Metallo
    • , Brian P Fiske
    • , Kevin D Courtney
    • , Scott Malstrom
    • , Tahsin M Khan
    • , Charles Kung
    • , Amanda P Skoumbourdis
    • , Henrike Veith
    • , Noel Southall
    • , Martin J Walsh
    • , Kyle R Brimacombe
    • , William Leister
    • , Sophia Y Lunt
    • , Zachary R Johnson
    • , Katharine E Yen
    • , Kaiko Kunii
    • , Shawn M Davidson
    • , Heather R Christofk
    • , Christopher P Austin
    • , James Inglese
    • , Marian H Harris
    • , John M Asara
    • , Gregory Stephanopoulos
    • , Francesco G Salituro
    • , Shengfang Jin
    • , Lenny Dang
    • , Douglas S Auld
    • , Hee-Won Park
    • , Lewis C Cantley
    • , Craig J Thomas
    •  & Matthew G Vander Heiden