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

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.

  • Posted in Nat Chem Biol, Publications
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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.

  • Posted in Nat Chem Biol, Publications
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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

  • Posted in Nat Chem Biol, Publications
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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

  • Posted in Nat Chem Biol, Publications
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Fourteen Ways to Reroute Cooperative Communication in the Lactose Repressor: Engineering Regulatory Proteins with Alternate Repressive Functions

September 14th, 2016 by David H. Richards, Sarai Meyer and Corey J. Wilson

TOC Graphic

ACS Synthetic Biology
DOI: 10.1021/acssynbio.6b00048
  • Posted in ACS Synthetic Biology, Publications
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The Influenza M2 Ectodomain Regulates the Conformational Equilibria of the Transmembrane Proton Channel: Insights from Solid-State Nuclear Magnetic Resonance

September 12th, 2016 by Byungsu Kwon and Mei Hong

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.6b00727

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.