title: Molecular dynamics of the salt dependence of a cold-adapted enzyme: endonuclease I.
abstract: The effects of salt on the stability of globular proteins have been known for a long time. In the present investigations, we shall focus on the effect of the salt ions upon the structure and the activity of the endonuclease I enzyme. In the present work, we shall focus on the relationship between ion position and the structural features of the Vibrio salmonicida (VsEndA) enzyme. We will concentrate on major questions such as: how can salt ions affect the molecular structure? What is the activity of the enzyme and which specific regions are directly involved? For that purpose, we will study the behaviour of the VsEndA over different salt concentrations using molecular dynamics (MD) simulations. We report the results of MD simulations of the endonuclease I enzyme at five different salt concentrations. Analysis of trajectories in terms of the root mean square fluctuation (RMSF), radial distribution function, contact numbers and hydrogen bonding lifetimes, indicate distinct differences when changing the concentration of NaCl. Results are found to be in good agreement with experimental data, where we have noted an optimum salt concentration for activity equal to 425 mM. Under this salt concentration, the VsEndA exhibits two more flexible loop regions, compared to the other salt concentrations. When analysing the RMSF of these two specific regions, three residues were selected for their higher mobility. We find a correlation between the structural properties studied here such as the radial distribution function, the contact numbers and the hydrogen bonding lifetimes, and the structural flexibility of only two polar residues. Finally, in the light of the present work, the molecular basis of the salt adaptation of VsEndA enzyme has been explored by mean of explicit solvent and salt treatment. Our results reveal that modulation of the sodium/chloride ions interaction with some specific loop regions of the protein is the strategy followed by this type of psychrophilic enzyme to enhance catalytic activity at the physiological conditions.
authors: a LCPM Laboratory, Faculty of Sciences, Chemistry Department , University of Oran , Oran , Algeria.
authors: D
authors: D
authors: Benrezkallah
authors: b SirMa CNRS UMR 7369 MEDyC , University of Reims Champagne Ardenne , Reims , France.
authors: M
authors: M
authors: Dauchez
authors: a LCPM Laboratory, Faculty of Sciences, Chemistry Department , University of Oran , Oran , Algeria.
authors: A M
authors: AM
authors: Krallafa
mesh_terms: D000595:Amino Acid Sequence; D003080:Cold Temperature; D003850:Deoxyribonuclease I / Q000737:chemistry*; D006860:Hydrogen Bonding; D007477:Ions / Q000737:chemistry; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D012492:Salts / Q000737:chemistry*; D012965:Sodium Chloride; D013329:Structure-Activity Relationship
chemical_list: D007477:Ions; D012492:Salts; D012965:Sodium Chloride; D003850:Deoxyribonuclease I
keywords: activity; molecular dynamics; salt dependence; structure