Intrinsic dynamics of restriction endonuclease EcoO109I studied by molecular dynamics simulations and X-ray scattering data analysis

Tomotaka Oroguchi, Hiroshi Hashimoto, Toshiyuki Shimizu, Mamoru Sato, Mitsunori Ikeguchi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

EcoO109I is a type II restriction endonuclease that functions as a dimer in solution. Upon DNA binding to the enzyme, the two subunits rotate counterclockwise relative to each other, as the two catalytic domains undergo structural changes to capture the cognate DNA. Using a 150-ns molecular dynamics simulation, we investigated the intrinsic dynamics of the DNA-free enzyme in solution to elucidate the relationship between enzyme dynamics and structural changes. The simulation revealed that the enzyme is considerably flexible, and thus exhibits large fluctuations in the radius of gyration. The small-angle x-ray scattering profile calculated from the simulation, including scattering from explicit hydration water, was in agreement with the experimentally observed profile. Principal component analysis revealed that the major dynamics were represented by the open-close and counterclockwise motions: the former is required for the enzyme to access DNA, whereas the latter corresponds to structural changes upon DNA binding. Furthermore, the intrinsic dynamics in the catalytic domains were consistent with motions capturing the cognate DNA. These results indicate that the structure of EcoO109I is intrinsically flexible in the direction of its functional movement, to facilitate effective structural changes for sequence-specific DNA recognition and processing.

Original languageEnglish
Pages (from-to)2808-2822
Number of pages15
JournalBiophysical Journal
Volume96
Issue number7
DOIs
Publication statusPublished - 2009
Externally publishedYes

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DNA Restriction Enzymes
Molecular Dynamics Simulation
X-Rays
DNA
Enzymes
Catalytic Domain
Type II Site Specific Deoxyribonucleases
Principal Component Analysis
Water

ASJC Scopus subject areas

  • Biophysics

Cite this

Intrinsic dynamics of restriction endonuclease EcoO109I studied by molecular dynamics simulations and X-ray scattering data analysis. / Oroguchi, Tomotaka; Hashimoto, Hiroshi; Shimizu, Toshiyuki; Sato, Mamoru; Ikeguchi, Mitsunori.

In: Biophysical Journal, Vol. 96, No. 7, 2009, p. 2808-2822.

Research output: Contribution to journalArticle

Oroguchi, Tomotaka ; Hashimoto, Hiroshi ; Shimizu, Toshiyuki ; Sato, Mamoru ; Ikeguchi, Mitsunori. / Intrinsic dynamics of restriction endonuclease EcoO109I studied by molecular dynamics simulations and X-ray scattering data analysis. In: Biophysical Journal. 2009 ; Vol. 96, No. 7. pp. 2808-2822.
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