Oligosaccharyltransferase inhibition induces senescence in RTK-driven tumor cells

October 3rd, 2016 by Cecilia Lopez-Sambrooks

Nature Chemical Biology 12, 1023 (2016). doi:10.1038/nchembio.2194

Authors: Cecilia Lopez-Sambrooks, Shiteshu Shrimal, Carol Khodier, Daniel P Flaherty, Natalie Rinis, Jonathan C Charest, Ningguo Gao, Peng Zhao, Lance Wells, Timothy A Lewis, Mark A Lehrman, Reid Gilmore, Jennifer E Golden & Joseph N Contessa

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Cbr1 is a Dph3 reductase required for the tRNA wobble uridine modification

October 3rd, 2016 by Zhewang Lin

Nature Chemical Biology 12, 995 (2016). doi:10.1038/nchembio.2190

Authors: Zhewang Lin, Min Dong, Yugang Zhang, Eunyoung Alisa Lee & Hening Lin

Diphthamide and the tRNA wobble uridine modifications both require diphthamide biosynthesis 3 (Dph3) protein as an electron donor for the iron-sulfur clusters in their biosynthetic enzymes. Here, using a proteomic approach, we identified Saccharomyces cerevisiae cytochrome b5 reductase (Cbr1) as a NADH-dependent reductase for Dph3. The NADH- and Cbr1-dependent reduction of Dph3 may provide a regulatory linkage between cellular metabolic state and protein translation.

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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.

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.

Proteasomes: Attack of cancer drugs

September 20th, 2016 by Mirella Bucci

Nature Chemical Biology 12, 763 (2016). doi:10.1038/nchembio.2198

Author: Mirella Bucci