Volume 14 Issue 11, November 2018

Volume 14 Issue 11

Preventing codon slippage

The cover depicts the structure of tRNAMet bearing an N 4-acetylcytidine (ac4C) modification at the first position of the anticodon. The acetyltransferase TmcAL introduces the ac4C modification, and loss of TmcAL results in misdecoding of the AUA codon.

See Taniguchi et al.

Image: Be Design Inc. Cover design: Erin Dewalt

Research Highlights

News & Views

  • News & Views |

    The prodrug dimethyloxalylglycine (DMOG) is a well-known tool compound used to study hypoxia. New findings reveal that DMOG also inhibits glutamine metabolism and can be exploited to selectively kill some cancer cells, highlighting important caveats when using DMOG for hypoxia studies.

    • Barbara S. Nelson
    • , Daniel M. Kremer
    •  & Costas A. Lyssiotis
  • News & Views |

    The proteome-wide application of a probe that selectively labels cysteine residues oxidized to the sulfinic acid form reveals the mammalian S-sulfinylome and uncovers novel substrates of the sulfinyl reductase sulfiredoxin, opening yet unexplored realms of cysteine-based redox regulation.

    • Sophie Rahuel-Clermont
    •  & Michel B. Toledano
  • News & Views |

    A Donnan equilibrium causes an influx of chloride ions into the Escherichia coli periplasm when the bacterium finds itself in gastric fluid. The combination of low pH and high anion concentration drives proteins to aggregate, a potentially lethal event unless prevented by specific chaperones.

    • Colin Kleanthous

Articles

  • Article |

    An electrophilic diazene probe (DiaAlk) enables capture and proteomic analysis of cysteine S-sulfinylation modifications, thus illuminating dynamic responses to oxidative stress and enabling the identification of new substrates of sulfiredoxin.

    • Salma Akter
    • , Ling Fu
    • , Youngeun Jung
    • , Mauro Lo Conte
    • , J. Reed Lawson
    • , W. Todd Lowther
    • , Rui Sun
    • , Keke Liu
    • , Jing Yang
    •  & Kate S. Carroll
  • Article |

    In response to the deletion of key genes involved in biosynthesis of the essential CoA precursor β-alanine, Escherichia coli overcomes this pathway damage by successively evolving alternative metabolic pathways.

    • Sammy Pontrelli
    • , Riley C. B. Fricke
    • , Shao Thing Teoh
    • , Walter A. Laviña
    • , Sastia Prama Putri
    • , Sorel Fitz-Gibbon
    • , Matthew Chung
    • , Matteo Pellegrini
    • , Eiichiro Fukusaki
    •  & James C. Liao
  • Article |

    A comparative genomic approach identified a novel acetate-dependent tRNA-modifying enzyme that catalyzes RNA acetylation with a mechanism similar to tRNA aminoacylation. This modification maintains decoding fidelity in protein synthesis.

    • Takaaki Taniguchi
    • , Kenjyo Miyauchi
    • , Yuriko Sakaguchi
    • , Seisuke Yamashita
    • , Akiko Soma
    • , Kozo Tomita
    •  & Tsutomu Suzuki
  • Article |

    mmBCFAs are endogenous fatty acids synthesized from BCAAs by brown and white adipose tissue via CrAT and FASN promiscuity. BCAA catabolism and mmBCFA lipogenesis are decreased by obesity-induced adipose hypoxia and influenced by the microbiome.

    • Martina Wallace
    • , Courtney R. Green
    • , Lindsay S. Roberts
    • , Yujung Michelle Lee
    • , Justin L. McCarville
    • , Joan Sanchez-Gurmaches
    • , Noah Meurs
    • , Jivani M. Gengatharan
    • , Justin D. Hover
    • , Susan A. Phillips
    • , Theodore P. Ciaraldi
    • , David A. Guertin
    • , Pedro Cabrales
    • , Janelle S. Ayres
    • , Daniel K. Nomura
    • , Rohit Loomba
    •  & Christian M. Metallo
  • Article |

    High intracellular concentrations of the α-ketoglutarate analog N-oxalylglycine, owing to MCT2-mediated transport of its newly described prodrug MOG, inhibit multiple enzymes in glutamine metabolism and selectively kill MCT2-expressing cancer cells.

    • Louise Fets
    • , Paul C. Driscoll
    • , Fiona Grimm
    • , Aakriti Jain
    • , Patrícia M. Nunes
    • , Michalis Gounis
    • , Ginevra Doglioni
    • , George Papageorgiou
    • , Timothy J. Ragan
    • , Sebastien Campos
    • , Mariana Silva dos Santos
    • , James I. MacRae
    • , Nicola O’Reilly
    • , Alan J. Wright
    • , Cyril H. Benes
    • , Kevin D. Courtney
    • , David House
    •  & Dimitrios Anastasiou
  • Article |

    Engineering of small-molecule-responsive RNA-binding proteins enables chemical regulation of modified mRNA or RNA replicon expression within mammalian cells for applications in synthetic circuit design and RNA-centered therapeutics.

    • Tyler E. Wagner
    • , Jacob R. Becraft
    • , Katie Bodner
    • , Brian Teague
    • , Xin Zhang
    • , Amanda Woo
    • , Ely Porter
    • , Bremy Alburquerque
    • , Brian Dobosh
    • , Oliwia Andries
    • , Niek N. Sanders
    • , Jacob Beal
    • , Douglas Densmore
    • , Tasuku Kitada
    •  & Ron Weiss
  • Article |

    Protonation of periplasmic protein carboxylic groups creates a Donnan equilibrium in the bacterial periplasmic space at low pH, leading to accumulation of Cl and unfolding and aggregation of periplasmic proteins, which can be rescued by chaperones.

    • Frederick Stull
    • , Hannah Hipp
    • , Randy B. Stockbridge
    •  & James C. A. Bardwell
  • Article |

    The active-state structure of a GPCR occupied by a partial agonist, β2AR with salmeterol, together with mutagenesis and biophysical studies, explains this ligand's unusual pharmacological profile.

    • Matthieu Masureel
    • , Yaozhong Zou
    • , Louis-Philippe Picard
    • , Emma van der Westhuizen
    • , Jacob P. Mahoney
    • , João P. G. L. M. Rodrigues
    • , Thomas J. Mildorf
    • , Ron O. Dror
    • , David E. Shaw
    • , Michel Bouvier
    • , Els Pardon
    • , Jan Steyaert
    • , Roger K. Sunahara
    • , William I. Weis
    • , Cheng Zhang
    •  & Brian K. Kobilka