title: A molecular mechanical analysis of the active site of urease with a special emphasis on determining the binding conformations available to oxygen-bound urea.
abstract: In order to model the active site of urease which contains two nickel ions with differing coordination geometries new parameters were derived for the AMBER* force field. These parameters were obtained by structure based optimization and use a single set of parameters with points on a sphere approach to model nickel(II) high-spin in all its coordination geometries. The force field was successfully used to model the active site of urease and to predict that a bridging water between the two nickel ions in urease was missing from the solid state structure of urease. A thorough conformational search was undertaken to find the conformations available to urea within urease. All the low energy conformations found were used to determine a consensus urea binding model.
authors.affiliation: Chemistry Department, Connecticut College, New London 06320, USA.
authors.forename: C
authors.initials: C
authors.lastname: Csiki
authors.forename: M
authors.initials: M
authors.lastname: Zimmer
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D008958:Models, Molecular; D009532:Nickel / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011487:Protein Conformation; D014508:Urea / Q000378:metabolism*; D014510:Urease / Q000737:chemistry* / Q000378:metabolism
chemical_list: D009532:Nickel; D014508:Urea; D014510:Urease; D010100:Oxygen