Crystal Structures of Apo and Metal-Bound Forms of the UreE Protein from Helicobacter pylori: Role of Multiple Metal Binding Sites

The crystal structure of the urease maturation protein UreE from Helicobacter pylori has been determined in its apo form at 2.1 angstrom resolution, bound to Cu2+ at 2.7 angstrom resolution, and bound to Ni2+ at 3.1 angstrom resolution. Apo UreE forms dimers, while the metal-hound enzymes are arranged as tetramers that consist of a dimer of dimers associated around the metal ion through coordination by His102 residues from each subunit of the tetramer. Comparison of independent subunits from different crystal forms indicates changes in the relative arrangement of the N- and C-terminal domains in response to metal binding. The improved ability of engineered versions of UreE containing hexahistidine sequences at either the N-terminal or C-terminal end to provide Ni2+ for the final metal sink (urease) is eliminated in the H102A version. Therefore, the ability of the improved Ni2+-binding versions to deliver more nickel is likely an effect of an increased local concentration of metal ions that can rapidly replenish transferred ions bound to His102.