Signal Transduction: Notch catches a Jagged edge

May 17th, 2017 by Stephen C Blacklow

Nature Chemical Biology 13, 570 (2017). doi:10.1038/nchembio.2379

Author: Stephen C Blacklow

Notch signaling is an essential cell–cell communication pathway that influences numerous cell fate decisions during development. Structural and biochemical studies of a Notch–Jagged complex dramatically advance current understanding of ligand recognition, and reveal evidence of catch-bond behavior in the complex.

Erratum: A Vibrio cholerae autoinducer–receptor pair that controls biofilm formation

May 17th, 2017 by Kai Papenfort

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

Author: Kai Papenfort, Justin E Silpe, Kelsey R Schramma, Jian-Ping Cong, Mohammad R Seyedsayamdost & Bonnie L Bassler

  • 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

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β-Lactone formation during product release from a nonribosomal peptide synthetase

May 15th, 2017 by Jason E Schaffer

Nature Chemical Biology 13, 737 (2017). doi:10.1038/nchembio.2374

Authors: Jason E Schaffer, Margaret R Reck, Neha K Prasad & Timothy A Wencewicz

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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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Autonomous Cell Migration to CSF1 Sources via a Synthetic Protein-Based System

May 10th, 2017 by Anam Qudrat and Kevin Truong

TOC Graphic

ACS Synthetic Biology
DOI: 10.1021/acssynbio.7b00076

Antibiotic resistance: Blocking tetracycline destruction

May 8th, 2017 by Sonja Petkovic

Nature Chemical Biology 13, 694 (2017). doi:10.1038/nchembio.2396

Authors: Sonja Petkovic & Winfried Hinrichs

Enzymology and structural and functional characterization of some FAD-dependent monooxygenases provide insights into degradation of tetracycline antibiotics, but also show unexpected features of substrate recognition, reaction mechanism, and competitive inhibition.

Membrane curvature regulates ligand-specific membrane sorting of GPCRs in living cells

May 8th, 2017 by Kadla R Rosholm

Nature Chemical Biology 13, 724 (2017). doi:10.1038/nchembio.2372

Authors: Kadla R Rosholm, Natascha Leijnse, Anna Mantsiou, Vadym Tkach, Søren L Pedersen, Volker F Wirth, Lene B Oddershede, Knud J Jensen, Karen L Martinez, Nikos S Hatzakis, Poul Martin Bendix, Andrew Callan-Jones & Dimitrios Stamou

  • Posted in Nat Chem Biol, Publications
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Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes

May 8th, 2017 by Jooyoung Park

Nature Chemical Biology 13, 730 (2017). doi:10.1038/nchembio.2376

Authors: Jooyoung Park, Andrew J Gasparrini, Margaret R Reck, Chanez T Symister, Jennifer L Elliott, Joseph P Vogel, Timothy A Wencewicz, Gautam Dantas & Niraj H Tolia

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