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.

  • Posted in Nat Chem Biol, Publications
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Biochemical Validation of a Third Guanidine Riboswitch Class in Bacteria

January 6th, 2017 by Madeline E. Sherlock and Ronald R. Breaker

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Biochemistry
DOI: 10.1021/acs.biochem.6b01271

Duration Control of Protein Expression in Vivo by Light-Mediated Reversible Activation of Translation

January 4th, 2017 by Shinzi Ogasawara

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ACS Chemical Biology
DOI: 10.1021/acschembio.6b00684
  • Posted in ACS Chemical Biology, Publications
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A Photoactivatable Innate Immune Receptor for Optogenetic Inflammation

December 29th, 2016 by Brittany A. Moser and Aaron P. Esser-Kahn

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ACS Chemical Biology
DOI: 10.1021/acschembio.6b01012

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

  • Posted in Nat Chem Biol, Publications
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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.

  • Posted in Nat Chem Biol, Publications
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RIT1 GTPase Regulates Sox2 Transcriptional Activity and Hippocampal Neurogenesis [Signal Transduction]

December 22nd, 2016 by Sajad Mir, Weikang Cai, Douglas A. Andres

Adult neurogenesis, the process of generating mature neurons from neuronal progenitor cells, makes critical contributions to neural circuitry and brain function under both healthy and disease states. Neurogenesis is a highly regulated process, in which diverse environmental and physiological stimuli are relayed to resident neural stem cell populations to control the transcription of genes involved in their self-renewal and differentiation. Understanding the molecular mechanisms governing neurogenesis is necessary for the development of translational strategies to harness this process for neuronal repair. Here we report that the Ras-related GTPase, RIT1, serves to control the sequential proliferation and differentiation of adult hippocampal neural/stem progenitor cells (NPCs), with in vivo expression of active RIT1 driving robust adult neurogenesis. Gene expression profiling analysis demonstrates increased expression of a specific set of transcription factors known to govern adult neurogenesis in response to active RIT1 expression in the hippocampus, including sex-determining region Y-related HMG box 2 (Sox2), a well-established regulator of stem cell self-renewal and neurogenesis. In adult hippocampal neuronal precursor cells (HNPCs), RIT1 controls an Akt-dependent signaling cascade, resulting in the stabilization and transcriptional activation of phosphorylated Sox2. Together, these studies support a role for RIT1 in relaying niche-derived signals to NPCs to control transcription of genes involved in self-renewal and differentiation.

Can Reduction of NO to N2O in Cytochrome c Dependent Nitric Oxide Reductase Proceed through a Trans-Mechanism?

December 21st, 2016 by Margareta R. A. Blomberg

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Biochemistry
DOI: 10.1021/acs.biochem.6b00788

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.

  • Posted in Nat Chem Biol, Publications
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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

  • Posted in Nat Chem Biol, Publications
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