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 [ (PUBMED:8318889) ]. They are believed to function as metallochaperones to deliver nickel to urease apoprotein [ (PUBMED:12072968) (PUBMED:10753863) ]. It has been shown by yeast two-hybrid analysis that UreE forms a dimeric complex with UreG in Helicobacter pylori [ (PUBMED:12388207) ]. The UreDFG-apoenzyme complex has also been shown to exist [ (PUBMED:11157956) (PUBMED:7721685) ] and is believed to be, with the addition of UreE, the assembly system for active urease [ (PUBMED:7721685) ]. 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 [ (PUBMED:11591723) (PUBMED: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 [ (PUBMED:15866948) ].
Family alignment:
There are 5988 UreE_N domains in 5988 proteins in SMART's nrdb database.
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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing UreE_N domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with UreE_N domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing UreE_N domain in the selected taxonomic class.
Crystal structure of Klebsiella aerogenes UreE, a nickel-bindingmetallochaperone for urease activation.
J Biol Chem. 2001; 276: 49359-64
Display abstract
UreE is proposed to be a metallochaperone that delivers nickel ions tourease during activation of this bacterial virulence factor. Wild-typeKlebsiella aerogenes UreE binds approximately six nickel ions perhomodimer, whereas H144*UreE (a functional C-terminal truncated variant)was previously reported to bind two. We determined the structure ofH144*UreE by multi-wavelength anomalous diffraction and refined it to 1.5A resolution. The present structure reveals an Hsp40-like peptide-bindingdomain, an Atx1-like metal-binding domain, and a flexible C terminus.Three metal-binding sites per dimer, defined by structural analysis ofCu-H144*UreE, are on the opposite face of the Atx1-like domain thanobserved in the copper metallochaperone. One metal bridges the twosubunits via the pair of His-96 residues, whereas the other two sitesinvolve metal coordination by His-110 and His-112 within each subunit. Incontrast to the copper metallochaperone mechanism involving thiol ligandexchanges between structurally similar chaperones and target proteins, wepropose that the Hsp40-like module interacts with urease apoprotein and/orother urease accessory proteins, while the Atx1-like domain delivershistidyl-bound nickel to the urease active site.