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 N-terminal domain is termed the peptide-binding domain. Deletion of this domain does not eliminate enzymatic activity, and the truncated protein can still activate urease .