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

Mireille Moutiez (1) , Emmanuelle Schmitt (2) , Jérôme Seguin (1) , Robert Thai (1) , Emmanuel Favry (1) , Pascal Belin (1) , Yves Mechulam (2) , Muriel Gondry (1)

1 Service d’Ingénierie Moléculaire des Protéines
2 BIOC - Laboratoire de Biochimie de l'Ecole polytechnique

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.

Domains: Life Sciences [q-bio]; Biochemistry, Molecular Biology

Mireille Moutiez, Emmanuelle Schmitt, Jérôme Seguin, Robert Thai, Emmanuel Favry, et al.. Unravelling the mechanism of non-ribosomal peptide synthesis by cyclodipeptide synthases.. Nature Communications, 2014, 5 (October), pp.5141. ⟨10.1038/ncomms6141⟩. ⟨hal-01098814⟩