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The Structure of FemXWv in Complex with a Peptidyl-RNA Conjugate: Mechanism of Aminoacyl Transfer from Ala-tRNAAla to Peptidoglycan Precursors

Authors

  • Dr. Matthieu Fonvielle,

    1. Laboratoire de Recherche Moléculaire sur les Antibiotiques, Centre de Recherche des Cordeliers, Equipe 12, INSERM, U872, 75006 Paris (France)
    2. Université Pierre et Marie Curie – Paris 6, UMR S 872, 15 rue de l'Ecole de Médecine, 75006 Paris (France)
    3. Université Paris Descartes, Sorbonne Paris Cité, UMR S 872, 75006 Paris (France)
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    • These authors contributed equally to this work.

  • Dr. Inés Li de La Sierra-Gallay,

    1. Fonction et Architecture des Assemblages Macromoléculaires, Institut de Biochimie et de Biophysique Moléculaire et Cellulaire, Université Paris-Sud, UMR 8619, 91405 Orsay (France)
    2. CNRS, UMR 8619, 91405 Orsay (France)
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    • These authors contributed equally to this work.

  • Dr. Afaf H. El-Sagheer,

    1. Chemistry Branch, Dept. of Science and Mathematics, Faculty of Petroleum and Mining Engineering, Suez University, Suez, 43721 (Egypt)
    2. School of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ (UK)
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  • Maxime Lecerf,

    1. Laboratoire de Recherche Moléculaire sur les Antibiotiques, Centre de Recherche des Cordeliers, Equipe 12, INSERM, U872, 75006 Paris (France)
    2. Université Pierre et Marie Curie – Paris 6, UMR S 872, 15 rue de l'Ecole de Médecine, 75006 Paris (France)
    3. Université Paris Descartes, Sorbonne Paris Cité, UMR S 872, 75006 Paris (France)
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  • Delphine Patin,

    1. Laboratoire des Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et de Biophysique Moléculaire et Cellulaire, Université Paris-Sud, UMR 8619, 91405 Orsay (France)
    2. CNRS, UMR 8619, 91405 Orsay (France)
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  • Dr. Dénia Mellal,

    1. Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, Université Paris Descartes, UMR 8601, 75270 Paris (France)
    2. CNRS, UMR 8601, 75270 Paris (France)
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  • Dr. Claudine Mayer,

    1. Laboratoire de Recherche Moléculaire sur les Antibiotiques, Centre de Recherche des Cordeliers, Equipe 12, INSERM, U872, 75006 Paris (France)
    2. Université Pierre et Marie Curie – Paris 6, UMR S 872, 15 rue de l'Ecole de Médecine, 75006 Paris (France)
    3. Université Paris Descartes, Sorbonne Paris Cité, UMR S 872, 75006 Paris (France)
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  • Dr. Didier Blanot,

    1. Laboratoire des Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et de Biophysique Moléculaire et Cellulaire, Université Paris-Sud, UMR 8619, 91405 Orsay (France)
    2. CNRS, UMR 8619, 91405 Orsay (France)
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  • Dr. Nittaya Gale,

    1. School of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ (UK)
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  • Dr. Tom Brown,

    1. School of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ (UK)
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  • Dr. Herman van Tilbeurgh,

    1. Fonction et Architecture des Assemblages Macromoléculaires, Institut de Biochimie et de Biophysique Moléculaire et Cellulaire, Université Paris-Sud, UMR 8619, 91405 Orsay (France)
    2. CNRS, UMR 8619, 91405 Orsay (France)
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  • Dr. Mélanie Ethève-Quelquejeu,

    Corresponding author
    1. Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, Université Paris Descartes, UMR 8601, 75270 Paris (France)
    2. CNRS, UMR 8601, 75270 Paris (France)
    • Mélanie Ethève-Quelquejeu, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, Université Paris Descartes, UMR 8601, 75270 Paris (France)

      Michel Arthur, Laboratoire de Recherche Moléculaire sur les Antibiotiques, Centre de Recherche des Cordeliers, Equipe 12, INSERM, U872, 75006 Paris (France)

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  • Dr. Michel Arthur

    Corresponding author
    1. Laboratoire de Recherche Moléculaire sur les Antibiotiques, Centre de Recherche des Cordeliers, Equipe 12, INSERM, U872, 75006 Paris (France)
    2. Université Pierre et Marie Curie – Paris 6, UMR S 872, 15 rue de l'Ecole de Médecine, 75006 Paris (France)
    3. Université Paris Descartes, Sorbonne Paris Cité, UMR S 872, 75006 Paris (France)
    • Mélanie Ethève-Quelquejeu, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, Université Paris Descartes, UMR 8601, 75270 Paris (France)

      Michel Arthur, Laboratoire de Recherche Moléculaire sur les Antibiotiques, Centre de Recherche des Cordeliers, Equipe 12, INSERM, U872, 75006 Paris (France)

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  • This work was supported by the European Community (EUR-INTAFAR, Project No. LSHM-CT-2004-512138, 6th PCRD), and the French Infrastructure for Integrated Structural Biology (FRISBI) ANR-10-INSB-05-01, and a UK BBSRC sLOLA grant to A.H.E.-S. and T.B. (BB/J001694/1 “Extending the boundaries of nucleic acid chemistry”). D.M. was supported by a research fellowship from the Région Ile-de-France. We thank the PROXIMA 1 staff for help with synchrotron data collection.

Abstract

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To gain insight into the catalytic mechanism of non-ribosomal amino acid transferases, peptidyl-RNA conjugates were synthesized for co-crystallization with FemXWv of Weissella viridescens, which transfers L-Ala from Ala-tRNAAla to the peptidoglycan precursor UDP-MurNAc-pentapeptide. The structure of the resulting complex and mutational studies revealed the mechanism by which FemXWv binds its substrates for substrate-assisted catalysis and stabilization of the tetrahedral intermediate.

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