Structural and functional role of nickel ions in urease by molecular dynamics simulation

Nickel ions play several roles in the biological processes of microorganisms and plants. Urease has a nickel-containing active site and catalyzes the hydrolysis of urea to yield ammonia and carbamate. In the present study, the role of nickel ions is examined using molecular dynamics simulations of the holo and apo forms. Nonbonded models used for the nickel ions provide good reproduction of the active-site structure as indicated in the crystallized structure. The results confirm that urease has a rigid active site in either its holo or its apo form. A new conformation of the flap is observed in apo urease. The connection between the metal center and His(α323) is proposed to be responsible for maintaining the flap conformation. The binding free energy of acetohydroxamic acid and urease is estimated using the molecular mechanics-generalized Born/surface area method. The binding free energy is primarily driven by electrostatic interactions in the presence of nickel ions. Normal mode analysis is employed to characterize the movements of the flap in apo urease.