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

Nature Chemical Biology volume 14, pages 428–430 (2018)Cite this article

Abstract

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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Acknowledgements

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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Author notes

  1. These authors contributed equally: Shogo Moria; Allan H. Pang.

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA

    Shogo Mori, Allan H. Pang, Taylor A. Lundy, Atefeh Garzan, Oleg V. Tsodikov & Sylvie Garneau-Tsodikova

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  1. Shogo Mori
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  2. Allan H. Pang
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  3. Taylor A. Lundy
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  4. Atefeh Garzan
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Contributions

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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Supplementary Tables 1–4 and Supplementary Figure 1–21

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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). https://doi.org/10.1038/s41589-018-0014-7

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