A single viral enzyme drives tRNA-dependent hypermodification of DNA at adenine
to the N6 position of adenine within double-stranded DNA. We uncover a second step where the glycyl-dA intermediate undergoes an on-base rearrangement to form 6-NcmdA. Examination of the proposed reaction pathways by quantum chemical calculations confirms the instability of acyl exocyclic groups at N6-adenine and reveals an energetically favorable orientation of 6-NcmdA that restores canonical base pairing. An X-ray structure confirms Mom is a member of the GNAT superfamily and suggests binding sites for both tRNA and DNA. Guided by the Mom structure and patterns of sequence conservation across metagenomic space, we show residues R111 and S124 are essential for catalysis. This work demonstrates that the Mom enzyme defines a new category of acetyltransferases utilizing charged tRNA to modify DNA.
Authors
- Elisabeth A. Raleigh (ORCID: https://orcid.org/0000-0003-0745-9925)
- Anton Slyvka (ORCID: https://orcid.org/0000-0002-3177-9040)
- Sean Lund (ORCID: https://orcid.org/0000-0003-1656-7979)
- Michael S. Kuska
- Matthias Bochtler (ORCID: https://orcid.org/0000-0001-7884-4463)
- Rebekah M. B. Silva (ORCID: https://orcid.org/0000-0002-9144-4939)
- Peter Weigele (ORCID: https://orcid.org/0000-0003-3696-4541)
- Krzysztof Skowronek (ORCID: https://orcid.org/0000-0001-9973-7085)
- Yan‐Jiun Lee (ORCID: https://orcid.org/0000-0001-7534-2302)
- Chudi Guan
Institutions
- New England Biolabs (United States) (US)
- International Institute of Molecular and Cell Biology (PL)
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences (PL)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-04-03
- DOI
- https://doi.org/10.1038/s41467-026-70671-1
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- New England Biolabs
- Indian Institute of Science
- Fundacja na rzecz Nauki Polskiej
- Infrastruktura PL-Grid
- Międzynarodowy Instytut Biologii Molekularnej i Komórkowej w Warszawie
- Deutsches Elektronen-Synchrotron
- Academic Computer Centre Cyfronet, AGH University of Science and Technology