Interdomain communication in the endonuclease/motor subunit of type I restriction-modification enzyme EcoR124I

Dhiraj Sinha, Katsiaryna Shamayeva, Vyas Ramasubramani, David Řeha, Vitali Bialevich, Morteza Khabiri, Alena Guzanová, Niv Milbar, Marie Weiserová, Eva Csefalvay, Jannette Carey, Rüdiger Ettrich

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Restriction-modification systems protect bacteria from foreign DNA. Type I restriction-modification enzymes are multifunctional heteromeric complexes with DNA-cleavage and ATP-dependent DNA translocation activities located on endonuclease/motor subunit HsdR. The recent structure of the first intact motor subunit of the type I restriction enzyme from plasmid EcoR124I suggested a mechanism by which stalled translocation triggers DNA cleavage via a lysine residue on the endonuclease domain that contacts ATP bound between the two helicase domains. In the present work, molecular dynamics simulations are used to explore this proposal. Molecular dynamics simulations suggest that the Lys-ATP contact alternates with a contact with a nearby loop housing the conserved QxxxY motif that had been implicated in DNA cleavage. This model is tested here using in vivo and in vitro experiments. The results indicate how local interactions are transduced to domain motions within the endonuclease/motor subunit.

Original languageEnglish (US)
Article number2334
JournalJournal of Molecular Modeling
Issue number7
StatePublished - Jul 2014

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Inorganic Chemistry
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Computational Theory and Mathematics
  • Organic Chemistry


  • Correlated loop motions
  • DNA restriction enzymes
  • E. coli
  • Molecular modeling
  • Multisubunit enzyme complex
  • Principal components analysis
  • QM/MM calculations


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