Metabolomics: Budgeting on a diet

October 20th, 2015 by Grant Miura

Nature Chemical Biology 11, 828 (2015). doi:10.1038/nchembio.1944

Author: Grant Miura

Polyketide synthase chimeras reveal key role of ketosynthase domain in chain branching

October 19th, 2015 by Srividhya Sundaram

Nature Chemical Biology 11, 949 (2015). doi:10.1038/nchembio.1932

Authors: Srividhya Sundaram, Daniel Heine & Christian Hertweck

Biosynthesis of rhizoxin in Burkholderia rhizoxinica affords an unusual polyketide synthase module with ketosynthase and branching domains that install the δ-lactone, conferring antimitotic activity. To investigate their functions in chain branching, we designed chimeric modules with structurally similar domains from a glutarimide-forming module and a dehydratase. Biochemical, kinetic and mutational analyses reveal a structural role of the accessory domains and multifarious catalytic actions of the ketosynthase.

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Chemical libraries: How dark is HTS dark matter?

October 19th, 2015 by Ricardo Macarron

Nature Chemical Biology 11, 904 (2015). doi:10.1038/nchembio.1937

Author: Ricardo Macarron

Selecting compounds for the chemical library is the foundation of high-throughput screening (HTS). After some years and multiple HTS campaigns, many molecules in the Novartis and NIH Molecular Libraries Program screening collections have never been found to be active. An in-depth exploration of the bioactivity of this 'dark matter' does in fact reveal some compounds of interest.

Dark chemical matter as a promising starting point for drug lead discovery

October 19th, 2015 by Anne Mai Wassermann

Nature Chemical Biology 11, 958 (2015). doi:10.1038/nchembio.1936

Authors: Anne Mai Wassermann, Eugen Lounkine, Dominic Hoepfner, Gaelle Le Goff, Frederick J King, Christian Studer, John M Peltier, Melissa L Grippo, Vivian Prindle, Jianshi Tao, Ansgar Schuffenhauer, Iain M Wallace, Shanni Chen, Philipp Krastel, Amanda Cobos-Correa, Christian N Parker, John W Davies & Meir Glick

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Mapping the energy landscape for second-stage folding of a single membrane protein

October 19th, 2015 by Duyoung Min

Nature Chemical Biology 11, 981 (2015). doi:10.1038/nchembio.1939

Authors: Duyoung Min, Robert E Jefferson, James U Bowie & Tae-Young Yoon

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MicroRNAs regulate the immunometabolic response to viral infection in the liver

October 19th, 2015 by Ragunath Singaravelu

Nature Chemical Biology 11, 988 (2015). doi:10.1038/nchembio.1940

Authors: Ragunath Singaravelu, Shifawn O'Hara, Daniel M Jones, Ran Chen, Nathan G Taylor, Prashanth Srinivasan, Curtis Quan, Dominic G Roy, Rineke H Steenbergen, Anil Kumar, Rodney K Lyn, Dennis Özcelik, Yanouchka Rouleau, My-Anh Nguyen, Katey J Rayner, Tom C Hobman, David Lorne Tyrrell, Rodney S Russell & John Paul Pezacki

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Light-assisted small-molecule screening against protein kinases

October 12th, 2015 by Álvaro Inglés-Prieto

Nature Chemical Biology 11, 952 (2015). doi:10.1038/nchembio.1933

Authors: Álvaro Inglés-Prieto, Eva Reichhart, Markus K Muellner, Matthias Nowak, Sebastian M B Nijman, Michael Grusch & Harald Janovjak

High-throughput live-cell screens are intricate elements of systems biology studies and drug discovery pipelines. Here, we demonstrate an optogenetics-assisted method that avoids the need for chemical activators and reporters, reduces the number of operational steps and increases information content in a cell-based small-molecule screen against human protein kinases, including an orphan receptor tyrosine kinase. This blueprint for all-optical screening can be adapted to many drug targets and cellular processes.

Determinants of amyloid fibril degradation by the PDZ protease HTRA1

October 5th, 2015 by Simon Poepsel

Nature Chemical Biology 11, 862 (2015). doi:10.1038/nchembio.1931

Authors: Simon Poepsel, Andreas Sprengel, Barbara Sacca, Farnusch Kaschani, Markus Kaiser, Christos Gatsogiannis, Stefan Raunser, Tim Clausen & Michael Ehrmann

New IDH1 mutant inhibitors for treatment of acute myeloid leukemia

October 5th, 2015 by Ujunwa C Okoye-Okafor

Nature Chemical Biology 11, 878 (2015). doi:10.1038/nchembio.1930

Authors: Ujunwa C Okoye-Okafor, Boris Bartholdy, Jessy Cartier, Enoch N Gao, Beth Pietrak, Alan R Rendina, Cynthia Rominger, Chad Quinn, Angela Smallwood, Kenneth J Wiggall, Alexander J Reif, Stanley J Schmidt, Hongwei Qi, Huizhen Zhao, Gerard Joberty, Maria Faelth-Savitski, Marcus Bantscheff, Gerard Drewes, Chaya Duraiswami, Pat Brady, Arthur Groy, Swathi-Rao Narayanagari, Iléana Antony-Debre, Kelly Mitchell, Heng Rui Wang, Yun-Ruei Kao, Maximilian Christopeit, Luis Carvajal, Laura Barreyro, Elisabeth Paietta, Hideki Makishima, Britta Will, Nestor Concha, Nicholas D Adams, Benjamin Schwartz, Michael T McCabe, Jaroslav Maciejewski, Amit Verma & Ulrich Steidl

Crystal structure of the Varkud satellite ribozyme

September 28th, 2015 by Nikolai B Suslov

Nature Chemical Biology 11, 840 (2015). doi:10.1038/nchembio.1929

Authors: Nikolai B Suslov, Saurja DasGupta, Hao Huang, James R Fuller, David M J Lilley, Phoebe A Rice & Joseph A Piccirilli