Urease. Recent insights in the role of nickel

Urease is the enzyme that catalyzes the hydrolysis of urea as the last step of organic nitrogen mineralization in the environmental nitrogen cycle. The two Ni(II) ions present in the active site are essential for this enzymatic reaction. This review describes and critically discusses the major advances in the understanding of the chemistry of the metal ions that have been achieved in the past 10 years, mainly through the application of high resolution X-ray crystallography. In particular, the structure of the enzyme in its native form is described, as well as the structure of the enzyme complexed with small un-reactive molecules mimicking the structure of the substrate and the transition state of the reaction, thus providing snapshots of the reaction mechanism. In addition, the discussion of the structures of urease complexed with competitive inhibitors provides further insights into the reactivity of the nickel ions in the active site. Overall, this information is used to discuss the chemical role of the nickel ions for this hydrolytic reaction, fundamental both in medicine as well as in agriculture.