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Structural basis for backbone N-methylation by an interrupted adenylation domain


Interrupted adenylation domains are enigmatic fusions, in which one enzyme is inserted into another to form a highly unusual bifunctional enzyme. We present the first crystal structure of an interrupted adenylation domain that reveals a unique embedded methyltransferase. The structure and functional data provide insight into how these enzymes N-methylate amino acid precursors en route to nonribosomal peptides.

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Fig. 1: Structure of TioS(A4aM4A4b).
Fig. 2: Catalytic activities of the A and the M domain of TioS(A4aM4A4b).


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This work was supported by a NSF CAREER Award MCB-1149427 (to S.G.-T.) and by startup funds from the College of Pharmacy at the University of Kentucky (to S.G.-T. and O.V.T.).

Author information




S.M., A.H.P., T.A.L., O.V.T., and S.G.-T. designed the study and wrote the manuscript. S.M. and T.A.L. performed biochemical experiments. A.H.P. performed crystallization and structure determination. A.G. performed chemical synthesis. S.M. and A.H.P. contributed equally.

Corresponding authors

Correspondence to Oleg V. Tsodikov or Sylvie Garneau-Tsodikova.

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The authors declare no competing interests.

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Mori, S., Pang, A.H., Lundy, T.A. et al. Structural basis for backbone N-methylation by an interrupted adenylation domain. Nat Chem Biol 14, 428–430 (2018).

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