Plant development: Get lit on steroids

May 17th, 2017 by Mirella Bucci

Nature Chemical Biology 13, 569 (2017). doi:10.1038/nchembio.2401

Author: Mirella Bucci

Synthetic biology: Return to sender

May 17th, 2017 by Grant Miura

Nature Chemical Biology 13, 569 (2017). doi:10.1038/nchembio.2398

Author: Grant Miura

Enzymology: Radical ring resizing

May 17th, 2017 by Caitlin Deane

Nature Chemical Biology 13, 569 (2017). doi:10.1038/nchembio.2399

Author: Caitlin Deane

Unraveling cell-to-cell signaling networks with chemical biology

May 17th, 2017 by Zev J Gartner

Nature Chemical Biology 13, 564 (2017). doi:10.1038/nchembio.2391

Authors: Zev J Gartner, Jennifer A Prescher & Luke D Lavis

Cell-to-cell signaling networks, although poorly understood, guide tissue development, regulate tissue function and may become dysregulated in disease. Chemical biologists can develop the next generation of tools to untangle these complex and dynamic networks of interacting cells.

Infectious disease: A lethal sugar fix

May 17th, 2017 by Alison Farrell

Nature Chemical Biology 13, 569 (2017). doi:10.1038/nchembio.2400

Author: Alison Farrell

Small-molecule phenotypic screening with stem cells

May 17th, 2017 by Andrei Ursu

Nature Chemical Biology 13, 560 (2017). doi:10.1038/nchembio.2383

Authors: Andrei Ursu, Hans R Schöler & Herbert Waldmann

To fully leverage the potential of human-induced pluripotent stem cells (hiPSCs), improved and standardized reprogramming methods and large-scale collections of hiPSC lines are needed, and the stem cell community must embrace chemical biology methodology for target identification and validation.

Erratum: Full antagonism of the estrogen receptor without a prototypical ligand side chain

May 17th, 2017 by Sathish Srinivasan

Nature Chemical Biology 13, 691 (2017). doi:10.1038/nchembio0617-691b

Author: Sathish Srinivasan, Jerome C Nwachukwu, Nelson E Bruno, Venkatasubramanian Dharmarajan, Devrishi Goswami, Irida Kastrati, Scott Novick, Jason Nowak, Valerie Cavett, Hai-Bing Zhou, Nittaya Boonmuen, Yuechao Zhao, Jian Min, Jonna Frasor, Benita S Katzenellenbogen, Patrick R Griffin, John A Katzenellenbogen & Kendall W Nettles

  • Posted in Nat Chem Biol, Publications
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H2S oxidation by nanodisc-embedded human sulfide quinone oxidoreductase [Enzymology]

May 16th, 2017 by Aaron P Landry, David P Ballou, Ruma Banerjee

Buildup of hydrogen sulfide (H2S), which functions as a signaling molecule but is toxic at high concentrations, is averted by its efficient oxidation by the mitochondrial sulfide oxidation pathway. The first step in this pathway is catalyzed by a flavoprotein, sulfide quinone oxidoreductase (SQR), which converts H2S to a persulfide and transfers electrons to coenzyme Q via a flavin cofactor. All previous studies on human SQR have used detergent-solubilized protein. Here, we embedded human SQR in nanodiscs (ndSQR) and studied highly homogenous preparations by steady-state and rapid kinetics techniques. ndSQR exhibited higher catalytic rates in its membranous environment than in its solubilized state. Stopped-flow spectroscopic data revealed that transfer of the sulfane sulfur from an SQR-bound cysteine persulfide intermediate to a small-molecule acceptor is the rate-limiting step. The physiological acceptor of sulfane sulfur from SQR has been the subject of controversy; we report that the kinetic analysis of ndSQR is consistent with glutathione rather than sulfite being the predominant acceptor at physiologically relevant concentrations of the respective metabolites. The identity of the acceptor has an important bearing on how the sulfide oxidation pathway is organized. Our data are more consistent with the following reaction sequence for sulfide oxidation: H2S→glutathione persulfide→sulfite→sulfate, than with a more convoluted route that would result if sulfite were the primary acceptor of sulfane sulfur. In summary, nanodisc-incorporated human SQR exhibits enhanced catalytic performance, and pre-steady state kinetic characterization of the complete SQR catalytic cycle indicates that GSH serves as the physiologically relevant sulfur acceptor.

A conserved threonine prevents self-intoxication of enoyl-thioester reductases

May 15th, 2017 by Raoul G Rosenthal

Nature Chemical Biology 13, 745 (2017). doi:10.1038/nchembio.2375

Authors: Raoul G Rosenthal, Bastian Vögeli, Tristan Wagner, Seigo Shima & Tobias J Erb

  • Posted in Nat Chem Biol, Publications
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Developing Spindlin1 small-molecule inhibitors by using protein microarrays

May 15th, 2017 by Narkhyun Bae

Nature Chemical Biology 13, 750 (2017). doi:10.1038/nchembio.2377

Authors: Narkhyun Bae, Monica Viviano, Xiaonan Su, Jie Lv, Donghang Cheng, Cari Sagum, Sabrina Castellano, Xue Bai, Claire Johnson, Mahmoud Ibrahim Khalil, Jianjun Shen, Kaifu Chen, Haitao Li, Gianluca Sbardella & Mark T Bedford

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