Non-classical transpeptidases yield insight into new antibacterials

November 7th, 2016 by Pankaj Kumar

Nature Chemical Biology 13, 54 (2017). doi:10.1038/nchembio.2237

Authors: Pankaj Kumar, Amit Kaushik, Evan P Lloyd, Shao-Gang Li, Rohini Mattoo, Nicole C Ammerman, Drew T Bell, Alexander L Perryman, Trevor A Zandi, Sean Ekins, Stephan L Ginell, Craig A Townsend, Joel S Freundlich & Gyanu Lamichhane

Genetic engineering: Chemical control for CRISPR editing

November 7th, 2016 by Isaac B Hilton

Nature Chemical Biology 13, 2 (2017). doi:10.1038/nchembio.2243

Authors: Isaac B Hilton & Charles A Gersbach

New approaches allow tight control over Cas9 activity using chemical induction. These studies expand the ability to rapidly induce and suppress Cas9-mediated nuclease activity and conditionally modulate the multiplex regulation of endogenous gene expression.

A multi-step peptidolytic cascade for amino acid recovery in chloroplasts

October 31st, 2016 by Pedro F Teixeira

Nature Chemical Biology 13, 15 (2017). doi:10.1038/nchembio.2227

Authors: Pedro F Teixeira, Beata Kmiec, Rui M M Branca, Monika W Murcha, Anna Byzia, Aneta Ivanova, James Whelan, Marcin Drag, Janne Lehtiö & Elzbieta Glaser

Plastids (including chloroplasts) are subcellular sites for a plethora of proteolytic reactions, required in functions ranging from protein biogenesis to quality control. Here we show that peptides generated from pre-protein maturation within chloroplasts of Arabidopsis thaliana are degraded to amino acids by a multi-step peptidolytic cascade consisting of oligopeptidases and aminopeptidases, effectively allowing the recovery of single amino acids within these organelles.

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Genome-wide genetic screening with chemically mutagenized haploid embryonic stem cells

October 31st, 2016 by Josep V Forment

Nature Chemical Biology 13, 12 (2017). doi:10.1038/nchembio.2226

Authors: Josep V Forment, Mareike Herzog, Julia Coates, Tomasz Konopka, Bianca V Gapp, Sebastian M Nijman, David J Adams, Thomas M Keane & Stephen P Jackson

In model organisms, classical genetic screening via random mutagenesis provides key insights into the molecular bases of genetic interactions, helping to define synthetic lethality, synthetic viability and drug-resistance mechanisms. The limited genetic tractability of diploid mammalian cells, however, precludes this approach. Here, we demonstrate the feasibility of classical genetic screening in mammalian systems by using haploid cells, chemical mutagenesis and next-generation sequencing, providing a new tool to explore mammalian genetic interactions.

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Multidimensional chemical control of CRISPR–Cas9

October 31st, 2016 by Basudeb Maji

Nature Chemical Biology 13, 9 (2017). doi:10.1038/nchembio.2224

Authors: Basudeb Maji, Christopher L Moore, Bernd Zetsche, Sara E Volz, Feng Zhang, Matthew D Shoulders & Amit Choudhary

Cas9-based technologies have transformed genome engineering and the interrogation of genomic functions, but methods to control such technologies across numerous dimensions—including dose, time, specificity, and mutually exclusive modulation of multiple genes—are still lacking. We conferred such multidimensional controls to diverse Cas9 systems by leveraging small-molecule-regulated protein degron domains. Application of our strategy to both Cas9-mediated genome editing and transcriptional activities opens new avenues for systematic genome interrogation.

Dereplication of peptidic natural products through database search of mass spectra

October 31st, 2016 by Hosein Mohimani

Nature Chemical Biology 13, 30 (2017). doi:10.1038/nchembio.2219

Authors: Hosein Mohimani, Alexey Gurevich, Alla Mikheenko, Neha Garg, Louis-Felix Nothias, Akihiro Ninomiya, Kentaro Takada, Pieter C Dorrestein & Pavel A Pevzner

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Profiling drugs for rheumatoid arthritis that inhibit synovial fibroblast activation

October 31st, 2016 by Douglas S Jones

Nature Chemical Biology 13, 38 (2017). doi:10.1038/nchembio.2211

Authors: Douglas S Jones, Anne P Jenney, Jennifer L Swantek, John M Burke, Douglas A Lauffenburger & Peter K Sorger

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Structure of p300 in complex with acyl-CoA variants

October 31st, 2016 by Zuzanna Kaczmarska

Nature Chemical Biology 13, 21 (2017). doi:10.1038/nchembio.2217

Authors: Zuzanna Kaczmarska, Esther Ortega, Afsaneh Goudarzi, He Huang, Sunjoo Kim, José A Márquez, Yingming Zhao, Saadi Khochbin & Daniel Panne

Potent and selective bivalent inhibitors of BET bromodomains

October 24th, 2016 by Michael J Waring

Nature Chemical Biology 12, 1097 (2016). doi:10.1038/nchembio.2210

Authors: Michael J Waring, Huawei Chen, Alfred A Rabow, Graeme Walker, Romel Bobby, Scott Boiko, Rob H Bradbury, Rowena Callis, Edwin Clark, Ian Dale, Danette L Daniels, Austin Dulak, Liz Flavell, Geoff Holdgate, Thomas A Jowitt, Alexey Kikhney, Mark McAlister, Jacqui Méndez, Derek Ogg, Joe Patel, Philip Petteruti, Graeme R Robb, Matthew B Robers, Sakina Saif, Natalie Stratton, Dmitri I Svergun, Wenxian Wang, David Whittaker, David M Wilson & Yi Yao

Small-molecule factor D inhibitors targeting the alternative complement pathway

October 24th, 2016 by Jürgen Maibaum

Nature Chemical Biology 12, 1105 (2016). doi:10.1038/nchembio.2208

Authors: Jürgen Maibaum, Sha-Mei Liao, Anna Vulpetti, Nils Ostermann, Stefan Randl, Simon Rüdisser, Edwige Lorthiois, Paul Erbel, Bernd Kinzel, Fabrice A Kolb, Samuel Barbieri, Julia Wagner, Corinne Durand, Kamal Fettis, Solene Dussauge, Nicola Hughes, Omar Delgado, Ulrich Hommel, Ty Gould, Aengus Mac Sweeney, Bernd Gerhartz, Frederic Cumin, Stefanie Flohr, Anna Schubart, Bruce Jaffee, Richard Harrison, Antonio Maria Risitano, Jörg Eder & Karen Anderson

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