Intrinsic Disorder: Fuzzy fast feedback

April 13th, 2017 by Mirella Bucci

Nature Chemical Biology 13, 451 (2017). doi:10.1038/nchembio.2367

Author: Mirella Bucci

Targeted protein degradation: You can glue it too!

April 13th, 2017 by Michal J Walczak

Nature Chemical Biology 13, 452 (2017). doi:10.1038/nchembio.2355

Authors: Michal J Walczak, Georg Petzold & Nicolas H Thomä

Proteolysis-targeting chimera (PROTACs) are synthetic molecules that recruit neo-substrate proteins to a ubiquitin ligase for ubiquitination and subsequent degradation. Structural insight into the VHL–MZ1–BRD4 complex reveals how the rationally designed MZ1–PROTAC molecule mediates degradation of an unnatural protein substrate.

Anti-Bacterials: Out-SMARting drug resistance

April 13th, 2017 by Alison Farrell

Nature Chemical Biology 13, 451 (2017). doi:10.1038/nchembio.2368

Author: Alison Farrell

The chemical basis for electrical signaling

April 13th, 2017 by William A Catterall

Nature Chemical Biology 13, 455 (2017). doi:10.1038/nchembio.2353

Authors: William A Catterall, Goragot Wisedchaisri & Ning Zheng

CRISPR–Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters

April 10th, 2017 by Mingzi M Zhang

Nature Chemical Biology 13, 607 (2017). doi:10.1038/nchembio.2341

Authors: Mingzi M Zhang, Fong Tian Wong, Yajie Wang, Shangwen Luo, Yee Hwee Lim, Elena Heng, Wan Lin Yeo, Ryan E Cobb, Behnam Enghiad, Ee Lui Ang & Huimin Zhao

Here we report an efficient CRISPR–Cas9 knock-in strategy to activate silent biosynthetic gene clusters (BGCs) in streptomycetes. We applied this one-step strategy to activate multiple BGCs of different classes in five Streptomyces species and triggered the production of unique metabolites, including a novel pentangular type II polyketide in Streptomyces viridochromogenes. This potentially scalable strategy complements existing activation approaches and facilitates discovery efforts to uncover new compounds with interesting bioactivities.

  • Posted in Nat Chem Biol, Publications
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Mechanistic insights into energy conservation by flavin-based electron bifurcation

April 10th, 2017 by Carolyn E Lubner

Nature Chemical Biology 13, 655 (2017). doi:10.1038/nchembio.2348

Authors: Carolyn E Lubner, David P Jennings, David W Mulder, Gerrit J Schut, Oleg A Zadvornyy, John P Hoben, Monika Tokmina-Lukaszewska, Luke Berry, Diep M Nguyen, Gina L Lipscomb, Brian Bothner, Anne K Jones, Anne-Frances Miller, Paul W King, Michael W W Adams & John W Peters

  • Posted in Nat Chem Biol, Publications
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Phosphorylated glycosphingolipids essential for cholesterol mobilization in Caenorhabditis elegans

April 3rd, 2017 by Sebastian Boland

Nature Chemical Biology 13, 647 (2017). doi:10.1038/nchembio.2347

Authors: Sebastian Boland, Ulrike Schmidt, Vyacheslav Zagoriy, Julio L Sampaio, Raphael F Fritsche, Regina Czerwonka, Tilo Lübken, Jakob Reimann, Sider Penkov, Hans-Joachim Knölker & Teymuras V Kurzchalia

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AtaT blocks translation initiation by N-acetylation of the initiator tRNAfMet

April 3rd, 2017 by Dukas Jurėnas

Nature Chemical Biology 13, 640 (2017). doi:10.1038/nchembio.2346

Authors: Dukas Jurėnas, Sneha Chatterjee, Albert Konijnenberg, Frank Sobott, Louis Droogmans, Abel Garcia-Pino & Laurence Van Melderen

  • Posted in Nat Chem Biol, Publications
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Insights into activity and inhibition from the crystal structure of human O-GlcNAcase

March 27th, 2017 by Nathaniel L Elsen

Nature Chemical Biology 13, 613 (2017). doi:10.1038/nchembio.2357

Authors: Nathaniel L Elsen, Sangita B Patel, Rachael E Ford, Dawn L Hall, Fred Hess, Hari Kandula, Maria Kornienko, John Reid, Harold Selnick, Jennifer M Shipman, Sujata Sharma, Kevin J Lumb, Stephen M Soisson & Daniel J Klein

O-GlcNAc hydrolase (OGA) catalyzes removal of βα-linked N-acetyl-D-glucosamine from serine and threonine residues. We report crystal structures of Homo sapiens OGA catalytic domain in apo and inhibited states, revealing a flexible dimer that displays three unique conformations and is characterized by subdomain α-helix swapping. These results identify new structural features of the substrate-binding groove adjacent to the catalytic site and open new opportunities for structural, mechanistic and drug discovery activities.

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Diabetes reversal by inhibition of the low-molecular-weight tyrosine phosphatase

March 27th, 2017 by Stephanie M Stanford

Nature Chemical Biology 13, 624 (2017). doi:10.1038/nchembio.2344

Authors: Stephanie M Stanford, Alexander E Aleshin, Vida Zhang, Robert J Ardecky, Michael P Hedrick, Jiwen Zou, Santhi R Ganji, Matthew R Bliss, Fusayo Yamamoto, Andrey A Bobkov, Janna Kiselar, Yingge Liu, Gregory W Cadwell, Shilpi Khare, Jinghua Yu, Antonio Barquilla, Thomas D Y Chung, Tomas Mustelin, Simon Schenk, Laurie A Bankston, Robert C Liddington, Anthony B Pinkerton & Nunzio Bottini

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