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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.).

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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.

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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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