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

• Published in: Journal of molecular modeling Vol. 20; no. 7; p. 2334
• Main Authors: Sinha, Dhiraj, Shamayeva, Katsiaryna, Ramasubramani, Vyas, Řeha, David, Bialevich, Vitali, Khabiri, Morteza, Guzanová, Alena, Milbar, Niv, Weiserová, Marie, Csefalvay, Eva, Carey, Jannette, Ettrich, Rüdiger
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-07-2014
• Subjects: Adenosine Triphosphate - chemistry; Adenosine Triphosphate - metabolism; Amino Acid Motifs; Binding Sites; Catalysis; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Computer Appl. in Life Sciences; Computer Applications in Chemistry; Conserved Sequence; Deoxyribonucleases, Type I Site-Specific - chemistry; Deoxyribonucleases, Type I Site-Specific - genetics; Deoxyribonucleases, Type I Site-Specific - metabolism; DNA - chemistry; DNA - metabolism; Genotype; Hydrolysis; Kinetics; Lysine; MIB 2013 (Modeling Interactions in Biomolecules VI); Molecular Dynamics Simulation; Molecular Medicine; Mutagenesis, Site-Directed; Mutation; Original Paper; Phenotype; Protein Binding; Protein Structure, Tertiary; Quantum Theory; Structure-Activity Relationship; Theoretical and Computational Chemistry; DNA restriction enzymes; QM/MM calculations; Principal components analysis; Multisubunit enzyme complex; Molecular modeling; Correlated loop motions
• ISSN: 1610-2940; 0948-5023
• DOI: 10.1007/s00894-014-2334-1

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.