Volume 14 Issue 7, July 2018

Volume 14 Issue 7

Metal on the mind

The cover depicts the distribution of copper in brain tissue slices of larval zebrafish, imaged using the fluorescent probe Copper Fluor-4 and stylized to appear as an oil painting. Rows depict various developmental stages of either wild-type or copper-deficient zebrafish, while columns depict anterior-to-posterior slices (left to right).

See Chang, C et al.

Image: Tong Xiao and Cheri Ackerman. Cover Design: Erin Dewalt

Research Highlights

News & Views

  • News & Views |

    Understanding how metals contribute to brain function is a major health priority. A new study combining pharmacology and genetics implicates the accumulation of copper in a brain arousal center as a regulator of zebrafish activity.

    • Jason Rihel
  • News & Views |

    The ability to subvert E3 ubiquitin ligases with small-molecule drugs offers tremendous promise for drug discovery. A new study demonstrates how structural and computational techniques can engineer and exploit unnatural protein–protein interfaces to design selective protein degraders.

    • Philip P. Chamberlain
  • News & Views |

    Single-molecule techniques combined with molecular dynamics simulations allowed visualization of a surprisingly high level of conformational homogeneity in the transport cycle of an ABC import system, BtuCD-F, and revealed an unexpected tight coupling of distinct conformational states responsible for vitamin B12 binding, transport and release.

    • Lutz Schmitt

Perspectives

Brief Communications

  • Brief Communication |

    The antibacterial microvionin contains two new lanthipeptide modifications, a triamino-dicarboxylic acid (avionin) and an N-terminal guanidino fatty acid, that lead to the establishment of the lipolanthine natural product class.

    • Vincent Wiebach
    • , Andi Mainz
    • , Mary-Ann J. Siegert
    • , Natalia A. Jungmann
    • , Guillaume Lesquame
    • , Sophie Tirat
    • , Assia Dreux-Zigha
    • , Jozsef Aszodi
    • , Dominique Le Beller
    •  & Roderich D. Süssmuth

Articles

  • Article |

    Copper contributes to regulating zebrafish rest–activity cycles through the locus coeruleus system by modulating the biosynthesis of norepinephrine; brain copper deficiency leads to lower levels of both synaptic norepinephrine and daytime activity.

    • Tong Xiao
    • , Cheri M. Ackerman
    • , Elizabeth C Carroll
    • , Shang Jia
    • , Adam Hoagland
    • , Jefferson Chan
    • , Bao Thai
    • , Christine S. Liu
    • , Ehud Y. Isacoff
    •  & Christopher J. Chang
  • Article |

    Computational protein design, without subsequent directed evolution, rapidly provides a set of aspartase variants capable of biocatalytic asymmetric addition of ammonia to substituted acrylates, producing various enantiopure β-amino acids.

    • Ruifeng Li
    • , Hein J. Wijma
    • , Lu Song
    • , Yinglu Cui
    • , Marleen Otzen
    • , Yu’e Tian
    • , Jiawei Du
    • , Tao Li
    • , Dingding Niu
    • , Yanchun Chen
    • , Jing Feng
    • , Jian Han
    • , Hao Chen
    • , Yong Tao
    • , Dick B. Janssen
    •  & Bian Wu
  • Article |

    Aided by the solving of the structures of human NMT1 with substrate-mimicking peptides, mapping of human and Arabidopsis myristoylomes defines a myristoylation recognition motif and over 1,000 myristoylated protein targets.

    • Benoit Castrec
    • , Cyril Dian
    • , Sarah Ciccone
    • , Coralie L. Ebert
    • , Willy V. Bienvenut
    • , Jean-Pierre Le Caer
    • , Jean-Marc Steyaert
    • , Carmela Giglione
    •  & Thierry Meinnel
  • Article |

    Structural, biochemical and cellular studies reveal JMJD7 to be a Jumonji-C oxygenase that catalyzes (3S)-lysyl hydroxylation of the translation factor family of GTPases, DRG1 and DRG2.

    • Suzana Markolovic
    • , Qinqin Zhuang
    • , Sarah E. Wilkins
    • , Charlotte D. Eaton
    • , Martine I. Abboud
    • , Maximiliano J. Katz
    • , Helen E. McNeil
    • , Robert K. Leśniak
    • , Charlotte Hall
    • , Weston B. Struwe
    • , Rebecca Konietzny
    • , Simon Davis
    • , Ming Yang
    • , Wei Ge
    • , Justin L. P. Benesch
    • , Benedikt M. Kessler
    • , Peter J. Ratcliffe
    • , Matthew E. Cockman
    • , Roman Fischer
    • , Pablo Wappner
    • , Rasheduzzaman Chowdhury
    • , Mathew L. Coleman
    •  & Christopher J. Schofield
  • Article |

    A bioinformatic strategy beginning with solute-binding proteins involved in sugar transport led to the functional annotation of four previously unknown catabolic pathways of the branched pentose d-apiose.

    • Michael S. Carter
    • , Xinshuai Zhang
    • , Hua Huang
    • , Jason T. Bouvier
    • , Brian San Francisco
    • , Matthew W. Vetting
    • , Nawar Al-Obaidi
    • , Jeffrey B. Bonanno
    • , Agnidipta Ghosh
    • , Rémi G. Zallot
    • , Harvey M. Andersen
    • , Steven C. Almo
    •  & John A. Gerlt
  • Article |

    Selectivity of ligand-induced protein degradation and dimerization is conferred by plastic interprotein contacts. Computational protein–protein docking reveals the underlying interprotein contacts to inform the design of a BRD4 selective degrader.

    • Radosław P. Nowak
    • , Stephen L. DeAngelo
    • , Dennis Buckley
    • , Zhixiang He
    • , Katherine A. Donovan
    • , Jian An
    • , Nozhat Safaee
    • , Mark P. Jedrychowski
    • , Charles M. Ponthier
    • , Mette Ishoey
    • , Tinghu Zhang
    • , Joseph D. Mancias
    • , Nathanael S. Gray
    • , James E. Bradner
    •  & Eric S. Fischer
  • Article |

    A single-molecule approach combined with molecular dynamics simulations to examine the conformational dynamics of the Escherichia coli ABC transporter BtuCD defines a coordinated sequence of events leading to unidirectional transport.

    • Min Yang
    • , Nurit Livnat Levanon
    • , Burçin Acar
    • , Burcu Aykac Fas
    • , Gal Masrati
    • , Jessica Rose
    • , Nir Ben-Tal
    • , Turkan Haliloglu
    • , Yongfang Zhao
    •  & Oded Lewinson
  • Article |

    Functional and structural characterization of PtmA2 reveals that it is an unusual non-adenylating acyl-CoA ligase and part of a system wherein the canonical acyl-CoA ligase reaction is separated into two half-reactions performed by distinct enzymes.

    • Nan Wang
    • , Jeffrey D. Rudolf
    • , Liao-Bin Dong
    • , Jerzy Osipiuk
    • , Catherine Hatzos-Skintges
    • , Michael Endres
    • , Chin-Yuan Chang
    • , Gyorgy Babnigg
    • , Andrzej Joachimiak
    • , George N. Phillips Jr
    •  & Ben Shen
  • Article |

    Although the conversion of (7S)-salutaridinol 7-O-acetate to thebaine can occur spontaneously, the identification of a thebaine synthase enzyme that catalyzes the reaction indicates how nature avoids the formation of labile hydroxylated byproducts.

    • Xue Chen
    • , Jillian M. Hagel
    • , Limei Chang
    • , Joseph E. Tucker
    • , Stacey A. Shiigi
    • , Yuora Yelpaala
    • , Hsiang-Yun Chen
    • , Rodrigo Estrada
    • , Jeffrey Colbeck
    • , Maria Enquist-Newman
    • , Ana B. Ibáñez
    • , Guillaume Cottarel
    • , Genevieve M. Vidanes
    •  & Peter J. Facchini