Parallel evolution of non-homologous isofunctional enzymes in methionine biosynthesis

June 5th, 2017 by Karine Bastard

Nature Chemical Biology 13, 858 (2017). doi:10.1038/nchembio.2397

Authors: Karine Bastard, Alain Perret, Aline Mariage, Thomas Bessonnet, Agnès Pinet-Turpault, Jean-Louis Petit, Ekaterina Darii, Pascal Bazire, Carine Vergne-Vaxelaire, Clémence Brewee, Adrien Debard, Virginie Pellouin, Marielle Besnard-Gonnet, François Artiguenave, Claudine Médigue, David Vallenet, Antoine Danchin, Anne Zaparucha, Jean Weissenbach, Marcel Salanoubat & Véronique de Berardinis

  • Posted in Nat Chem Biol, Publications
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Autocatalytic backbone N-methylation in a family of ribosomal peptide natural products

June 5th, 2017 by Niels S van der Velden

Nature Chemical Biology 13, 833 (2017). doi:10.1038/nchembio.2393

Authors: Niels S van der Velden, Noemi Kälin, Maximilian J Helf, Jörn Piel, Michael F Freeman & Markus Künzler

Peptide backbone N-methylation, as seen in cyclosporin A, has been considered to be exclusive to nonribosomal peptides. We have identified the first post-translationally modified peptide or protein harboring internal α-N-methylations through discovery of the genetic locus for the omphalotins, cyclic N-methylated peptides produced by the fungus Omphalotus olearius. We show that iterative autocatalytic activity of an N-methyltransferase fused to its peptide substrate is the signature of a new family of ribosomally encoded metabolites.

  • Posted in Nat Chem Biol, Publications
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Remote Perturbations in Tertiary Contacts Trigger Ligation of Lysine to the Heme Iron in Cytochrome c

May 31st, 2017 by Jie Gu, Dong-Woo Shin and Ekaterina V. Pletneva

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Biochemistry
DOI: 10.1021/acs.biochem.6b01187

Lipid II overproduction allows direct assay of transpeptidase inhibition by β-lactams

May 29th, 2017 by Yuan Qiao

Nature Chemical Biology 13, 793 (2017). doi:10.1038/nchembio.2388

Authors: Yuan Qiao, Veerasak Srisuknimit, Frederick Rubino, Kaitlin Schaefer, Natividad Ruiz, Suzanne Walker & Daniel Kahne

  • Posted in Nat Chem Biol, Publications
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Structural and functional characterization of the hydrogenase-maturation HydF protein

May 29th, 2017 by Giorgio Caserta

Nature Chemical Biology 13, 779 (2017). doi:10.1038/nchembio.2385

Authors: Giorgio Caserta, Ludovic Pecqueur, Agnieszka Adamska-Venkatesh, Cecilia Papini, Souvik Roy, Vincent Artero, Mohamed Atta, Edward Reijerse, Wolfgang Lubitz & Marc Fontecave

  • Posted in Nat Chem Biol, Publications
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Functional selectivity of GPCR-directed drug action through location bias

May 29th, 2017 by Roshanak Irannejad

Nature Chemical Biology 13, 799 (2017). doi:10.1038/nchembio.2389

Authors: Roshanak Irannejad, Veronica Pessino, Delphine Mika, Bo Huang, Philip B Wedegaertner, Marco Conti & Mark von Zastrow

  • Posted in Nat Chem Biol, Publications
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Targeting S-adenosylmethionine biosynthesis with a novel allosteric inhibitor of Mat2A

May 29th, 2017 by Casey L Quinlan

Nature Chemical Biology 13, 785 (2017). doi:10.1038/nchembio.2384

Authors: Casey L Quinlan, Stephen E Kaiser, Ben Bolaños, Dawn Nowlin, Rita Grantner, Shannon Karlicek-Bryant, Jun Li Feng, Stephen Jenkinson, Kevin Freeman-Cook, Stephen G Dann, Xiaoli Wang, Peter A Wells, Valeria R Fantin, Al E Stewart & Stephan K Grant

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Structural basis for high-affinity fluorophore binding and activation by RNA Mango

May 29th, 2017 by Robert J Trachman

Nature Chemical Biology 13, 807 (2017). doi:10.1038/nchembio.2392

Authors: Robert J Trachman, Natalia A Demeshkina, Matthew W L Lau, Shanker Shyam S Panchapakesan, Sunny C Y Jeng, Peter J Unrau & Adrian R Ferré-D'Amaré

  • Posted in Nat Chem Biol, Publications
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Deamidation Slows Curli Amyloid-Protein Aggregation

May 26th, 2017 by Hanliu Wang, Qin Shu, Carl Frieden and Michael L. Gross

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.7b00241

Endoplasmic Reticulum Stress-induced Degradation of DNAJB12 Stimulates BOK Accumulation and Primes Cancer Cells for Apoptosis [Cell Biology]

May 23rd, 2017 by Pattarawut Sopha, Hong Yu Ren, Diane E. Grove, Douglas M Cyr

DNAJB12 (JB12) is an endoplasmic reticulum (ER)-associated Hsp40 family protein that recruits Hsp70 to the ER surface to coordinate the function of ER-associated and cytosolic chaperone systems in protein quality control. Hsp70 is stress inducible, but paradoxically, we report here that JB12 was degraded by the proteasome during severe ER stress. Destabilized JB12 was degraded by ER-associated degradation (ERAD) complexes that contained HERP, Sel1L, and gp78. JB12 was the only ER-associated chaperone that was destabilized by reductive stress. JB12 knockdown by siRNA led to the induction of Caspase processing, but not the unfolded protein response. ER stress-induced apoptosis is regulated by the highly labile and ER associated BCL-2 family member BOK, which is controlled at the level of protein stability by ERAD components. We found that JB12 was required in Huh-7 liver cancer cells to maintain BOK at low levels and BOK was detected in complexes with JB12 and gp78. Depletion of JB12 during reductive stress or by shRNA from Huh-7 cells was associated with accumulation of BOK, and activation of Caspase 3, 7, and 9. Absence of JB12 sensitized Huh-7 to death caused by proteotoxic agents and the proapoptotic chemotherapeutic LCL-161. In summary, JB12 is a stress sensitive Hsp40 whose degradation during severe ER stress provides a mechanism to promote BOK accumulation and induction of apoptosis.