Volume 16 Issue 7, July 2020

Volume 16 Issue 7

Generating the barrier

The cover depicts conformational dynamics of a short disordered segment of the monomeric yeast prion protein Sup35. This segment modulates the species-specific seeding activity, and a methylene group alone within a side chain of a glutamine residue is sufficient to drastically alter the species specificity of prion transmission.

See Shida et al.

IMAGE: Art Action Inc., Takaya Fukui. COVER DESIGN: Erin Dewalt

Obituary

  • Obituary |

    Rolf Huisgen left us on 26 March 2020, just three months shy of his 100th birthday. His work has had an enormous influence on chemical biology, ranging from new methods for the synthesis of chemical probes to “click chemistry” and its application to in vivo bioconjugation.

    • Dirk Trauner

Research Highlights

News & Views

  • News & Views |

    Glucose 6-phosphate dehydrogenase (G6PD) stands at the head of the pentose phosphate pathway, which is responsible for nucleotide synthesis. The identification and thorough validation of an improved G6PD inhibitor provide a valuable new tool compound for studying metabolism.

    • Michael E. Pacold
  • News & Views |

    The enzyme 5-lipoxygenase (5-LOX) initiates the biosynthesis of leukotrienes (LT), potent mediators of the inflammatory response. The first crystal structures of two complexes of inhibitor bound to 5-LOX reveal the functional consequences of the binding, including a change in the regiospecificity toward a 12/15-lipoxygenating enzyme.

    • Homero Rubbo
    •  & Irene Wood

Review Articles

Articles

  • Article |

    Domain insertion into the loop region of AcrIIC1 leads to a variant with enhanced inhibitory activity toward Neisseria meningitides Cas9, while structure-guided design turns AcrIIC1 into a potent inhibitor of Staphylococcus aureus Cas9.

    • Jan Mathony
    • , Zander Harteveld
    • , Carolin Schmelas
    • , Julius Upmeier zu Belzen
    • , Sabine Aschenbrenner
    • , Wei Sun
    • , Mareike D. Hoffmann
    • , Christina Stengl
    • , Andreas Scheck
    • , Sandrine Georgeon
    • , Stéphane Rosset
    • , Yanli Wang
    • , Dirk Grimm
    • , Roland Eils
    • , Bruno E. Correia
    •  & Dominik Niopek
  • Article |

    Identification of an improved glucose-6-phosphate dehydrogenase (G6PD) inhibitor G6PDi-1 blocks G6PD activity more robustly than the widely cited antagonist DHEA. G6PDi-1 treatment blocks T cell cytokine production and neutrophil oxidative burst.

    • Jonathan M. Ghergurovich
    • , Juan C. García-Cañaveras
    • , Joshua Wang
    • , Emily Schmidt
    • , Zhaoyue Zhang
    • , Tara TeSlaa
    • , Harshel Patel
    • , Li Chen
    • , Emily C. Britt
    • , Marta Piqueras-Nebot
    • , Mari Carmen Gomez-Cabrera
    • , Agustín Lahoz
    • , Jing Fan
    • , Ulf H. Beier
    • , Hahn Kim
    •  & Joshua D. Rabinowitz
  • Article |

    Evolution of a group of plant cellulose synthase-like enzymes into specialized glycosyltransferases in the endoplasmic reticulum membrane confers the ability to glucuronidate triterpenoid saponins and other specialized metabolites.

    • Adam Jozwiak
    • , Prashant D. Sonawane
    • , Sayantan Panda
    • , Constantine Garagounis
    • , Kalliope K. Papadopoulou
    • , Bekele Abebie
    • , Hassan Massalha
    • , Efrat Almekias-Siegl
    • , Tali Scherf
    •  & Asaph Aharoni
  • Article |

    A negative allosteric modulator of the G-protein-coupled receptor β2-adrenergic receptor binds to a membrane-facing surface adjacent to a molecular switch for receptor activation, and its binding disrupts a water-mediated polar network stabilizing an inactive switch conformation.

    • Xiangyu Liu
    • , Jonas Kaindl
    • , Magdalena Korczynska
    • , Anne Stößel
    • , Daniela Dengler
    • , Markus Stanek
    • , Harald Hübner
    • , Mary J. Clark
    • , Jake Mahoney
    • , Rachel Ann Matt
    • , Xinyu Xu
    • , Kunio Hirata
    • , Brian K. Shoichet
    • , Roger K. Sunahara
    • , Brian K. Kobilka
    •  & Peter Gmeiner
  • Article |

    The side chain interaction within the short disordered segment of yeast prion protein Sup35 could affect the conformation of the main chain, alter the transmission barrier between species and regulate its cross-seeding activity.

    • Toshinobu Shida
    • , Yuji O. Kamatari
    • , Takao Yoda
    • , Yoshiki Yamaguchi
    • , Michael Feig
    • , Yumiko Ohhashi
    • , Yuji Sugita
    • , Kazuo Kuwata
    •  & Motomasa Tanaka
  • Article |

    Cellular glycosylation facilitates molecular recognition of cells and biomolecules. A two-step N-glycan editing method enables selective glycoform ‘deletion’ and ‘insertion’ of new glycans, which can be used to probe their biological functions.

    • Feng Tang
    • , Mang Zhou
    • , Ken Qin
    • , Wei Shi
    • , Ansor Yashinov
    • , Yang Yang
    • , Liyun Yang
    • , Dongliang Guan
    • , Lei Zhao
    • , Yubo Tang
    • , Yujie Chang
    • , Lifen Zhao
    • , Huaiyu Yang
    • , Hu Zhou
    • , Ruimin Huang
    •  & Wei Huang
  • Article |

    Structures of the ketosynthase–chain length factor complex from ishigamide biosynthesis, cross-linked to the acyl carrier protein, reveal the molecular interactions between these domains and how the reaction pocket limits rounds of product extension.

    • Danyao Du
    • , Yohei Katsuyama
    • , Masanobu Horiuchi
    • , Shinya Fushinobu
    • , Aochiu Chen
    • , Tony D. Davis
    • , Michael D. Burkart
    •  & Yasuo Ohnishi
  • Article |

    Structures of 5-lipoxygenase (5-LOX) reveal that NDGA disturbs regions that shield the active site while AKBA binds an allosteric site. NDGA inhibits 5-LOX activity using its redox-active function, while AKBA changes the enzyme’s regiospecificity

    • Nathaniel C. Gilbert
    • , Jana Gerstmeier
    • , Erin E. Schexnaydre
    • , Friedemann Börner
    • , Ulrike Garscha
    • , David B. Neau
    • , Oliver Werz
    •  & Marcia E. Newcomer
  • Article |

    Drug combinations consisting of two cell death-targeting drugs are enriched for antagonism and ‘single-agent dominance’, where the faster-acting drug suppresses the slower-acting drug due to inhibitory crosstalk between cell death pathways.

    • Ryan Richards
    • , Hannah R. Schwartz
    • , Megan E. Honeywell
    • , Mariah S. Stewart
    • , Peter Cruz-Gordillo
    • , Anna J. Joyce
    • , Benjamin D. Landry
    •  & Michael J. Lee

Amendments & Corrections