Stapled peptides: How to be quick on the uptake

September 20th, 2016 by Joshua A Kritzer

Nature Chemical Biology 12, 764 (2016). doi:10.1038/nchembio.2183

Author: Joshua A Kritzer

Stapled helices are promising compounds for inhibiting intracellular protein–protein interactions, but the discovery of peptides with the key property of cellular uptake has taken place largely through trial and error. A new study defines physicochemical parameters for designing hydrocarbon-stapled helices with a greater likelihood of cellular uptake.

Phospholipids: How to flip a flippase

September 20th, 2016 by Caitlin Deane

Nature Chemical Biology 12, 763 (2016). doi:10.1038/nchembio.2199

Author: Caitlin Deane

Compounds that select against the tetracycline-resistance efflux pump

September 19th, 2016 by Laura K Stone

Nature Chemical Biology 12, 902 (2016). doi:10.1038/nchembio.2176

Authors: Laura K Stone, Michael Baym, Tami D Lieberman, Remy Chait, Jon Clardy & Roy Kishony

We developed a competition-based screening strategy to identify compounds that invert the selective advantage of antibiotic resistance. Using our assay, we screened over 19,000 compounds for the ability to select against the TetA tetracycline-resistance efflux pump in Escherichia coli and identified two hits, β-thujaplicin and disulfiram. Treating a tetracycline-resistant population with β-thujaplicin selects for loss of the resistance gene, enabling an effective second-phase treatment with doxycycline.

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Carbon extension in peptidylnucleoside biosynthesis by radical SAM enzymes

September 19th, 2016 by Edward A Lilla

Nature Chemical Biology 12, 905 (2016). doi:10.1038/nchembio.2187

Authors: Edward A Lilla & Kenichi Yokoyama

Nikkomycins and polyoxins are antifungal peptidylnucleoside antibiotics active against human and plant pathogens. Here we report that during peptidylnucleoside biosynthesis in Streptomyces cacaoi and S. tendae, the C5′ extension of the nucleoside essential for downstream structural diversification is catalyzed by a conserved radical S-adenosyl-L-methionine (SAM) enzyme, PolH or NikJ. This is distinct from the nucleophilic mechanism reported for antibacterial nucleosides and represents a new mechanism of nucleoside natural product biosynthesis.

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Engineering prokaryotic transcriptional activators as metabolite biosensors in yeast

September 19th, 2016 by Mette L Skjoedt

Nature Chemical Biology 12, 951 (2016). doi:10.1038/nchembio.2177

Authors: Mette L Skjoedt, Tim Snoek, Kanchana R Kildegaard, Dushica Arsovska, Michael Eichenberger, Tobias J Goedecke, Arun S Rajkumar, Jie Zhang, Mette Kristensen, Beata J Lehka, Solvej Siedler, Irina Borodina, Michael K Jensen & Jay D Keasling

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Ultra-deep tyrosine phosphoproteomics enabled by a phosphotyrosine superbinder

September 19th, 2016 by Yangyang Bian

Nature Chemical Biology 12, 959 (2016). doi:10.1038/nchembio.2178

Authors: Yangyang Bian, Lei Li, Mingming Dong, Xuguang Liu, Tomonori Kaneko, Kai Cheng, Huadong Liu, Courtney Voss, Xuan Cao, Yan Wang, David Litchfield, Mingliang Ye, Shawn S-C Li & Hanfa Zou

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The role of protein dynamics in the evolution of new enzyme function

September 12th, 2016 by Eleanor Campbell

Nature Chemical Biology 12, 944 (2016). doi:10.1038/nchembio.2175

Authors: Eleanor Campbell, Miriam Kaltenbach, Galen J Correy, Paul D Carr, Benjamin T Porebski, Emma K Livingstone, Livnat Afriat-Jurnou, Ashley M Buckle, Martin Weik, Florian Hollfelder, Nobuhiko Tokuriki & Colin J Jackson

A chemical-inducible CRISPR–Cas9 system for rapid control of genome editing

September 12th, 2016 by Kaiwen Ivy Liu

Nature Chemical Biology 12, 980 (2016). doi:10.1038/nchembio.2179

Authors: Kaiwen Ivy Liu, Muhammad Nadzim Bin Ramli, Cheok Wei Ariel Woo, Yuanming Wang, Tianyun Zhao, Xiujun Zhang, Guo Rong Daniel Yim, Bao Yi Chong, Ali Gowher, Mervyn Zi Hao Chua, Jonathan Jung, Jia Hui Jane Lee & Meng How Tan

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Lactate metabolism is associated with mammalian mitochondria

September 12th, 2016 by Ying-Jr Chen

Nature Chemical Biology 12, 937 (2016). doi:10.1038/nchembio.2172

Authors: Ying-Jr Chen, Nathaniel G Mahieu, Xiaojing Huang, Manmilan Singh, Peter A Crawford, Stephen L Johnson, Richard W Gross, Jacob Schaefer & Gary J Patti

How the glycosyltransferase OGT catalyzes amide bond cleavage

September 12th, 2016 by John Janetzko

Nature Chemical Biology 12, 899 (2016). doi:10.1038/nchembio.2173

Authors: John Janetzko, Sunia A Trauger, Michael B Lazarus & Suzanne Walker

The essential human enzyme O-linked β-N-acetylglucosamine transferase (OGT), known for modulating the functions of nuclear and cytoplasmic proteins through serine and threonine glycosylation, was unexpectedly implicated in the proteolytic maturation of the cell cycle regulator host cell factor-1 (HCF-1). Here we show that HCF-1 cleavage occurs via glycosylation of a glutamate side chain followed by on-enzyme formation of an internal pyroglutamate, which undergoes spontaneous backbone hydrolysis.