Nickel trafficking: insights into the fold and function of UreE, a urease metallochaperone

UreE is a metallo-chaperone assisting the incorporation of two adjacent Ni(2+) ions in the active site of urease. This study describes an attempt to distill general information on this protein using a computational post-genomic approach for the understanding of the structural details of the molecular function of UreE in nickel trafficking. The two crystal structures recently determined for UreE from Bacillus pasteurii (BpUreE) and Klebsiella aerogenes (KaUreE) were comparatively analyzed. This analysis provided insights into the protein structural and conformational features. A structural database of UreE proteins from a large number of different genomes was built using homology modeling. All available sequences of UreE were retrieved from protein and cDNA databases, and their structures were modeled on the crystal structures of BpUreE and KaUreE. A self-consistent iterative protocol was devised for multiple sequence alignment optimization involving secondary structure prediction and evaluation of the energy features of the obtained modeled structures. The quality of all models was tested using standard assessment procedures. The final optimized structure-based multiple alignment and the derived model structures provided insightful information on the evolutionary conservation of key residues in the protein sequence and surface patches presumably involved in protein recognition during the urease active site assembly.