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Unravelling the mechanism of non-ribosomal peptide synthesis by cyclodipeptide synthases

Author

Listed:
  • Mireille Moutiez

    (Service d’Ingénierie Moléculaire des Protéines, iBiTec-S, Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA))

  • Emmanuelle Schmitt

    (Laboratoire de Biochimie, Unité mixte de Recherche 7654, Ecole Polytechnique, Centre National de la Recherche Scientifique)

  • Jérôme Seguin

    (Service d’Ingénierie Moléculaire des Protéines, iBiTec-S, Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA))

  • Robert Thai

    (Service d’Ingénierie Moléculaire des Protéines, iBiTec-S, Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA))

  • Emmanuel Favry

    (Service d’Ingénierie Moléculaire des Protéines, iBiTec-S, Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA))

  • Pascal Belin

    (Service d’Ingénierie Moléculaire des Protéines, iBiTec-S, Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA))

  • Yves Mechulam

    (Laboratoire de Biochimie, Unité mixte de Recherche 7654, Ecole Polytechnique, Centre National de la Recherche Scientifique)

  • Muriel Gondry

    (Service d’Ingénierie Moléculaire des Protéines, iBiTec-S, Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA))

Abstract

Cyclodipeptide synthases form cyclodipeptides from two aminoacyl transfer RNAs. They use a ping-pong mechanism that begins with transfer of the aminoacyl moiety of the first aminoacyl tRNA onto a conserved serine, yielding an aminoacyl enzyme. Combining X-ray crystallography, site-directed mutagenesis and affinity labelling of the cyclodipeptide synthase AlbC, we demonstrate that the covalent intermediate reacts with the aminoacyl moiety of the second aminoacyl tRNA, forming a dipeptidyl enzyme, and identify the aminoacyl-binding sites of the aminoacyl tRNAs.

Suggested Citation

  • Mireille Moutiez & Emmanuelle Schmitt & Jérôme Seguin & Robert Thai & Emmanuel Favry & Pascal Belin & Yves Mechulam & Muriel Gondry, 2014. "Unravelling the mechanism of non-ribosomal peptide synthesis by cyclodipeptide synthases," Nature Communications, Nature, vol. 5(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6141
    DOI: 10.1038/ncomms6141
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