Explaining Urease Specificity Towards Nickel: A Re-Analysis of Its Proposed Mechanism

Urease is a binuclear metalloenzyme selective towards nickel, exhibiting a remarkable rate enhancement of the catalytic reaction. The accepted mechanism for urease describes the coordination of urea to both nickel centers in an O,N bridged mode, enabling the attack of the carbonyl by a bridged hydroxide present between the metallic centers. However, the substitution of nickel by other metals significantly reduces urease´s catalytic efficiency. The proposed mechanism cannot explain this difference in activity since it does not follow a rational nucleophilicity scale. After a careful analysis of the literature data on thermodynamics, kinetics, inhibition, and mutations, we verified that by analyzing the mechanism from a diffrent angle, another pathway is most likely occuring. This mechanism can explain urease´s selectivity towards nickel and all the data present in the literature, gathering amost a century of study about urease.