Amino-group carrier-protein-mediated secondary metabolite biosynthesis in Streptomyces

September 26th, 2016 by Fumihito Hasebe

Nature Chemical Biology 12, 967 (2016). doi:10.1038/nchembio.2181

Authors: Fumihito Hasebe, Kenichi Matsuda, Taro Shiraishi, Yushi Futamura, Takeshi Nakano, Takeo Tomita, Ken Ishigami, Hikari Taka, Reiko Mineki, Tsutomu Fujimura, Hiroyuki Osada, Tomohisa Kuzuyama & Makoto Nishiyama

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Thermal profiling reveals phenylalanine hydroxylase as an off-target of panobinostat

September 26th, 2016 by Isabelle Becher

Nature Chemical Biology 12, 908 (2016). doi:10.1038/nchembio.2185

Authors: Isabelle Becher, Thilo Werner, Carola Doce, Esther A Zaal, Ina Tögel, Crystal A Khan, Anne Rueger, Marcel Muelbaier, Elsa Salzer, Celia R Berkers, Paul F Fitzpatrick, Marcus Bantscheff & Mikhail M Savitski

We describe a two-dimensional thermal proteome profiling strategy that can be combined with an orthogonal chemoproteomics approach to enable comprehensive target profiling of the marketed histone deacetylase inhibitor panobinostat. The N-hydroxycinnamide moiety is identified as critical for potent and tetrahydrobiopterin-competitive inhibition of phenylalanine hydroxylase leading to increases in phenylalanine and decreases in tyrosine levels. These findings provide a rationale for adverse clinical observations and suggest repurposing of the drug for treatment of tyrosinemia.

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Structural basis for precursor protein–directed ribosomal peptide macrocyclization

September 26th, 2016 by Kunhua Li

Nature Chemical Biology 12, 973 (2016). doi:10.1038/nchembio.2200

Authors: Kunhua Li, Heather L Condurso, Gengnan Li, Yousong Ding & Steven D Bruner

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Roger Y. Tsien 1952–2016

September 26th, 2016 by Amy E Palmer

Nature Chemical Biology 12, 887 (2016). doi:10.1038/nchembio.2213

Authors: Amy E Palmer & Jin Zhang

Roger Tsien left us on August 24. His untimely passing has saddened and shocked the scientific community. Roger literally and figuratively brightened our world, illuminated the dark matter of biology, and forever changed our view of the interface of chemistry and biology.

Single-molecule biophysics: TALEs spin along, but not around

September 20th, 2016 by Sebastian Becker

Nature Chemical Biology 12, 766 (2016). doi:10.1038/nchembio.2182

Authors: Sebastian Becker & Jens Boch

TALE proteins search for target sequences along a DNA substrate in a uniquely one-dimensional and non-rotating fashion.

Host–microbe interactions: DAO does it

September 20th, 2016 by Mirella Bucci

Nature Chemical Biology 12, 763 (2016). doi:10.1038/nchembio.2196

Author: Mirella Bucci

Corrigendum: Structural biology: HDAC6 finally crystal clear

September 20th, 2016 by Yanli Liu

Nature Chemical Biology 12, 885 (2016). doi:10.1038/nchembio1016-885

Author: Yanli Liu, Li Li & Jinrong Min

Post-translational modifications: Bonds that bind

September 20th, 2016 by Marcey L Waters

Nature Chemical Biology 12, 768 (2016). doi:10.1038/nchembio.2186

Author: Marcey L Waters

Scientists find that oxidation of methionine induces favorable interactions with aromatic groups in proteins, contrary to conventional wisdom, providing new molecular insight into the structural and biological impact of methionine oxidation.

Transcriptional regulation: Stuck in traffic

September 20th, 2016 by Grant Miura

Nature Chemical Biology 12, 763 (2016). doi:10.1038/nchembio.2197

Author: Grant Miura

Transcriptional kinases: Caught by a sticky drug

September 20th, 2016 by Dalibor Blazek

Nature Chemical Biology 12, 765 (2016). doi:10.1038/nchembio.2184

Author: Dalibor Blazek

A new study reports THZ531 as a covalent CDK12/CDK13 inhibitor affecting transcription. Application of the compound in cells decreases transcription elongation of DNA damage response genes and key super-enhancer-associated transcription factor genes, with important implications for targeted cancer therapy.