A conserved phosphatase destroys toxic glycolytic side products in mammals and yeast

June 13th, 2016 by François Collard

Nature Chemical Biology 12, 601 (2016). doi:10.1038/nchembio.2104

Authors: François Collard, Francesca Baldin, Isabelle Gerin, Jennifer Bolsée, Gaëtane Noël, Julie Graff, Maria Veiga-da-Cunha, Vincent Stroobant, Didier Vertommen, Amina Houddane, Mark H Rider, Carole L Linster, Emile Van Schaftingen & Guido T Bommer

  • Posted in Nat Chem Biol, Publications
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Dual Function of Phosphoubiquitin in Activation of Parkin [Molecular Bases of Disease]

June 9th, 2016 by Walinda, E., Morimoto, D., Sugase, K., Shirakawa, M.

Mutations in the gene encoding parkin, an auto-inhibited E3 ubiquitin ligase that functions in the clearance of damaged mitochondria, are the most common cause of autosomal recessive juvenile Parkinsonism. The mechanism regulating parkin activation remains poorly understood. Here we show, by using isothermal titration calorimetry, solution NMR and fluorescence spectroscopy, that parkin can bind ubiquitin and phosphomimetic ubiquitin by recognizing the canonical hydrophobic patch and C-terminus of ubiquitin. The affinity of parkin for both phosphomimetic and unmodified ubiquitin is markedly enhanced upon removal of the ubiquitin-like (UBL) domain of parkin. This suggests that the agonistic binding of ubiquitin to parkin in trans is counterbalanced by the antagonistic activity of the parkin UBL domain in cis. Intriguingly, UBL binding is enthalpy-driven, whereas ubiquitin binding is driven by an increase in the total entropy of the system. These thermodynamic differences are explained by different chemistry in the ubiquitin- and UBL- binding pockets of parkin and, as shown by molecular dynamics simulations, are not a consequence of changes in protein conformational entropy. Indeed, comparison of conformational fluctuations reveals that the RING1-IBR element becomes considerably more rigid upon complex formation. A model of parkin activation is proposed in which E2~Ub binding triggers large-scale diffusional motion of the RING2 domain toward the ubiquitin-stabilized RING1-IBR assembly to complete formation of the active parkin/E2~Ub transfer complex. Thus, ubiquitin plays a dual role in parkin activation by competing with the inhibitory UBL domain and stabilizing the active form of parkin.

Real-time intravital imaging of pH variation associated with osteoclast activity

June 6th, 2016 by Hiroki Maeda

Nature Chemical Biology 12, 579 (2016). doi:10.1038/nchembio.2096

Authors: Hiroki Maeda, Toshiyuki Kowada, Junichi Kikuta, Masayuki Furuya, Mai Shirazaki, Shin Mizukami, Masaru Ishii & Kazuya Kikuchi

  • Posted in Nat Chem Biol, Publications
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Copper regulates cyclic-AMP-dependent lipolysis

June 6th, 2016 by Lakshmi Krishnamoorthy

Nature Chemical Biology 12, 586 (2016). doi:10.1038/nchembio.2098

Authors: Lakshmi Krishnamoorthy, Joseph A Cotruvo, Jefferson Chan, Harini Kaluarachchi, Abigael Muchenditsi, Venkata S Pendyala, Shang Jia, Allegra T Aron, Cheri M Ackerman, Mark N Vander Wal, Timothy Guan, Lukas P Smaga, Samouil L Farhi, Elizabeth J New, Svetlana Lutsenko & Christopher J Chang

Role of Ca2+ in the Stability and Function of TMEM16F and 16K

June 3rd, 2016 by Kenji Ishihara, Jun Suzuki and Shigekazu Nagata

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Biochemistry
DOI: 10.1021/acs.biochem.6b00176

σ1 receptor ligands control a switch between passive and active threat responses

May 30th, 2016 by Andrew J Rennekamp

Nature Chemical Biology 12, 552 (2016). doi:10.1038/nchembio.2089

Authors: Andrew J Rennekamp, Xi-Ping Huang, You Wang, Samir Patel, Paul J Lorello, Lindsay Cade, Andrew P W Gonzales, Jing-Ruey Joanna Yeh, Barbara J Caldarone, Bryan L Roth, David Kokel & Randall T Peterson

  • Posted in Nat Chem Biol, Publications
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Zebrafish behavioral profiling identifies multitarget antipsychotic-like compounds

May 30th, 2016 by Giancarlo Bruni

Nature Chemical Biology 12, 559 (2016). doi:10.1038/nchembio.2097

Authors: Giancarlo Bruni, Andrew J Rennekamp, Andrea Velenich, Matthew McCarroll, Leo Gendelev, Ethan Fertsch, Jack Taylor, Parth Lakhani, Dennis Lensen, Tama Evron, Paul J Lorello, Xi-Ping Huang, Sabine Kolczewski, Galen Carey, Barbara J Caldarone, Eric Prinssen, Bryan L Roth, Michael J Keiser, Randall T Peterson & David Kokel

  • Posted in Nat Chem Biol, Publications
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Mitochondrial DNA repair and replication proteins revealed by targeted chemical probes

May 30th, 2016 by Simon Wisnovsky

Nature Chemical Biology 12, 567 (2016). doi:10.1038/nchembio.2102

Authors: Simon Wisnovsky, Sae Rin Jean & Shana O Kelley

  • Posted in Nat Chem Biol, Publications
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pH-Dependent DNA Distortion and Repression of Gene Expression by Pectobacterium atrosepticum PecS

May 27th, 2016 by Dinesh K. Deochand, Jacob K. Meariman and Anne Grove

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ACS Chemical Biology
DOI: 10.1021/acschembio.6b00168
  • Posted in ACS Chemical Biology, Publications
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Advances in Enzymatic Glycoside Synthesis

May 26th, 2016 by Phillip M. Danby and Stephen G. Withers

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ACS Chemical Biology
DOI: 10.1021/acschembio.6b00340