Urease and other nickel metalloenzymes are synthesised as precursors devoid of the metalloenzyme active site. These precursors then undergo a complex post-translational maturation process that requires a number of accessory proteins.
Members of this group are nickel-binding proteins required for urease metallocentre assembly . They are believed to function as metallochaperones to deliver nickel to urease apoprotein [12072968, 10753863]. It has been shown by yeast two-hybrid analysis that UreE forms a dimeric complex with UreG in Helicobacter pylori . The UreDFG-apoenzyme complex has also been shown to exist [11157956, 7721685] and is believed to be, with the addition of UreE, the assembly system for active urease . The complexes, rather than the individual proteins, presumably bind to UreB via UreE/H recognition sites.
The structure of Klebsiella aerogenes UreE reveals a unique two-domain architecture.The N-terminal domain is structurally related to a heat shock protein, while the C-terminal domain shows homology to the Atx1 copper metallochaperone [11591723, 11602602]. Significantly, the metal-binding sites in UreE and Atx1 are distinct in location and types of residues despite the relationship between these proteins and the mechanism for UreE activation of urease is proposed to be different from the thiol ligand exchange mechanism used by the copper metallochaperones.
The C-terminal domain of this protein is the metal-binding region, which can bind up to six Ni molecules per dimer. Most members of this group contain a histidine-rich C-terminal motif that is involved in, but not solely responsible for, binding nickel ions in Klebsiella aerogenes UreE . However, internal ligands, not the histidine residues at the C terminus, are necessary for UreE to assist in urease activation in Klebsiella aerogenes , even though the truncated protein lacking the His-rich region binds two nickel ions instead of six. In Helicobacter pylori and some other organisms, the terminal histidine-rich binding sites are absent, but the internal histidine sites are present, and the latter probably function as nickel donors. Deletion analysis shows that this domain alone is sufficient for metal-binding and activation of urease .