MraY–antibiotic complex reveals details of tunicamycin mode of action

January 9th, 2017 by Jonna K Hakulinen

Nature Chemical Biology 13, 265 (2017). doi:10.1038/nchembio.2270

Authors: Jonna K Hakulinen, Jenny Hering, Gisela Brändén, Hongming Chen, Arjan Snijder, Margareta Ek & Patrik Johansson

The rapid increase of antibiotic resistance has created an urgent need to develop novel antimicrobial agents. Here we describe the crystal structure of the promising bacterial target phospho-N-acetylmuramoyl–pentapeptide translocase (MraY) in complex with the nucleoside antibiotic tunicamycin. The structure not only reveals the mode of action of several related natural-product antibiotics but also gives an indication on the binding mode of the MraY UDP–MurNAc–pentapeptide and undecaprenyl-phosphate substrates.

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Orthogonal lipid sensors identify transbilayer asymmetry of plasma membrane cholesterol

December 26th, 2016 by Shu-Lin Liu

Nature Chemical Biology 13, 268 (2017). doi:10.1038/nchembio.2268

Authors: Shu-Lin Liu, Ren Sheng, Jae Hun Jung, Li Wang, Ewa Stec, Matthew J O'Connor, Seohyoen Song, Rama Kamesh Bikkavilli, Robert A Winn, Daesung Lee, Kwanghee Baek, Kazumitsu Ueda, Irena Levitan, Kwang-Pyo Kim & Wonhwa Cho

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β2-adrenergic receptor control of endosomal PTH receptor signaling via Gβγ

December 26th, 2016 by Frédéric G Jean-Alphonse

Nature Chemical Biology 13, 259 (2017). doi:10.1038/nchembio.2267

Authors: Frédéric G Jean-Alphonse, Vanessa L Wehbi, Jingming Chen, Masaki Noda, Juan M Taboas, Kunhong Xiao & Jean-Pierre Vilardaga

Cells express several G-protein-coupled receptors (GPCRs) at their surfaces, transmitting simultaneous extracellular hormonal and chemical signals into cells. A comprehensive understanding of mechanisms underlying the integrated signaling response induced by distinct GPCRs is thus required. Here we found that the β2-adrenergic receptor, which induces a short cAMP response, prolongs nuclear cAMP and protein kinase A (PKA) activation by promoting endosomal cAMP production in parathyroid hormone (PTH) receptor signaling through the stimulatory action of G protein Gβγ subunits on adenylate cyclase type 2.

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Molecular insights into the enzyme promiscuity of an aromatic prenyltransferase

December 19th, 2016 by Ridao Chen

Nature Chemical Biology 13, 226 (2017). doi:10.1038/nchembio.2263

Authors: Ridao Chen, Bingquan Gao, Xiao Liu, Feiying Ruan, Yong Zhang, Jizhong Lou, Keping Feng, Carsten Wunsch, Shu-Ming Li, Jungui Dai & Fei Sun

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A fluorescent probe for cysteine depalmitoylation reveals dynamic APT signaling

December 19th, 2016 by Rahul S Kathayat

Nature Chemical Biology 13, 150 (2017). doi:10.1038/nchembio.2262

Authors: Rahul S Kathayat, Pablo D Elvira & Bryan C Dickinson

Hundreds of human proteins are modified by reversible palmitoylation of cysteine residues (S-palmitoylation), but the regulation of depalmitoylation is poorly understood. Here, we develop 'depalmitoylation probes' (DPPs), small-molecule fluorophores, to monitor the endogenous activity levels of 'erasers' of S-palmitoylation, acylprotein thioesterases (APTs). Live-cell analysis with DPPs reveals rapid growth-factor-mediated inhibition of the depalmitoylation activity of APTs, exposing a novel regulatory mechanism of dynamic lipid signaling.

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Inhibitors of Mycobacterium tuberculosis DosRST signaling and persistence

December 19th, 2016 by Huiqing Zheng

Nature Chemical Biology 13, 218 (2017). doi:10.1038/nchembio.2259

Authors: Huiqing Zheng, Christopher J Colvin, Benjamin K Johnson, Paul D Kirchhoff, Michael Wilson, Katriana Jorgensen-Muga, Scott D Larsen & Robert B Abramovitch

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Orphan receptor ligand discovery by pickpocketing pharmacological neighbors

December 19th, 2016 by Tony Ngo

Nature Chemical Biology 13, 235 (2017). doi:10.1038/nchembio.2266

Authors: Tony Ngo, Andrey V Ilatovskiy, Alastair G Stewart, James L J Coleman, Fiona M McRobb, R Peter Riek, Robert M Graham, Ruben Abagyan, Irina Kufareva & Nicola J Smith

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Protein folding: Minimizing frustration

December 16th, 2016 by Mirella Bucci

Nature Chemical Biology 13, 1 (2017). doi:10.1038/nchembio.2277

Author: Mirella Bucci

Biocatalysis: Custom carbon cycling

December 16th, 2016 by Caitlin Deane

Nature Chemical Biology 13, 1 (2017). doi:10.1038/nchembio.2275

Author: Caitlin Deane

Neurodegeneration: Untangling tau

December 16th, 2016 by Alison Farrell

Nature Chemical Biology 13, 1 (2017). doi:10.1038/nchembio.2276

Author: Alison Farrell