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

0437252 - ÚVGZ 2015 RIV US eng J - Článek v odborném periodiku
Sinha, Dhiraj - Shamayeva, Katerina - Ramasubramani, V. - Řeha, David - Bialevich, V. - Khabiri, Morteza - Guzanová, Alena - Milbar, N. - Weiserová, Marie - Cséfalvay, Eva - Carey, J. - Ettrich, Rüdiger
Interdomain communication in the endonuclease/motor subunit of type I restriction-modification enzyme EcoR124I.
Journal of Molecular Modeling. Roč. 20, č. 7 (2014), s. 2334. ISSN 1610-2940. E-ISSN 0948-5023
Grant CEP: GA ČR GAP207/12/2323
Institucionální podpora: RVO:67179843 ; RVO:61388971
Klíčová slova: DNA restriction enzymes * Molecular modeling * QM/MM calculations * principal components analysis * E. coli * Multisubunit enzyme complex * Correlated loop motions
Kód oboru RIV: EH - Ekologie - společenstva; EE - Mikrobiologie, virologie (MBU-M)
Impakt faktor: 1.736, rok: 2014

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.
Trvalý link: http://hdl.handle.net/11104/0240850