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

  • Posted in Nat Chem Biol, Publications
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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

  • Posted in Nat Chem Biol, Publications
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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

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

  • Posted in Nat Chem Biol, Publications
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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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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.

Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases

May 1st, 2017 by Linda Lauinger

Nature Chemical Biology 13, 709 (2017). doi:10.1038/nchembio.2370

Authors: Linda Lauinger, Jing Li, Anton Shostak, Ibrahim Avi Cemel, Nati Ha, Yaru Zhang, Philipp E Merkl, Simon Obermeyer, Nicolas Stankovic-Valentin, Tobias Schafmeier, Walter J Wever, Albert A Bowers, Kyle P Carter, Amy E Palmer, Herbert Tschochner, Frauke Melchior, Raymond J Deshaies, Michael Brunner & Axel Diernfellner

  • Posted in Nat Chem Biol, Publications
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Computational design of ligand-binding membrane receptors with high selectivity

May 1st, 2017 by Xiang Feng

Nature Chemical Biology 13, 715 (2017). doi:10.1038/nchembio.2371

Authors: Xiang Feng, Joaquin Ambia, Kuang-Yui M Chen, Melvin Young & Patrick Barth

  • Posted in Nat Chem Biol, Publications
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Reactive Oxygen Species Production Induced by Pore Opening in Cardiac Mitochondria: The Role of Complex II [Bioenergetics]

April 27th, 2017 by Paavo Korge, Scott A John, Guillaume Calmettes, James N Weiss

Succinate-driven reverse electron transport (RET) through complex I is hypothesized be a major source of ROS that induce permeability transition pore (PTP) opening and damage the heart during ischemia/reperfusion. Since RET can only generate ROS when mitochondria are fully polarized, however, this mechanism is self-limiting once PTP open during reperfusion. In the companion manuscript, we showed that ROS production after PTP opening can be sustained when complex III is damaged (simulated by antimycin). Here we show that complex II can also contribute to sustained ROS production in isolated rabbit cardiac mitochondria following inner membrane pore formation induced by either alamethicin or Ca-induced PTP opening. Two conditions are required to maximize malonate-sensitive ROS production by complex II in isolated mitochondria: a) complex II inhibition by atpenin A5 or complex III inhibition by stigmatellin that results in succinate-dependent reduction of the dicarboxylate binding site of complex II (site IIf ); b) pore opening in the inner membrane resulting in rapid efflux of succinate/fumarate and other dicarboxylates capable of competitively binding to site IIf. The decrease in matrix [dicarboxylates] allows O2 access to reduced site IIf, thereby making electron donation to O2 possible, explaining the rapid increase in ROS production provided that site IIf is reduced. Because ischemia is known to inhibit complexes II and III and increase matrix succinate/fumarate levels, we hypothesize that by allowing dicarboxylate efflux from the matrix, PTP opening during reperfusion may activate sustained ROS production by this mechanism after RET-driven ROS production has ceased.