Nickel proteins as enzymes, biosensors and trafficking shuttles: the urease story

Nickel is both a toxic and an essential component of the active site of several enzymes. Urease, a Ni2+-enzyme of high relevance for human health and agriculture, is the final destination of the greater part of the intracellular Ni2+. The mechanisms that regulate Ni2+ trafficking leading to urease activation represent a paradigm to understand the general principles of cellular Ni2+ homeostasis. NikR is a metal-sensor that responds to different concentrations of intracellular Ni2+, controlling the transcription of the urease operon: the latest insights into metal-binding and DNA-binding of the Ni2+ sensor NikR will be illustrated. The mechanism of Ni2+ delivery into the apo-urease precursor will be described on the basis of the available information on the urease accessory proteins UreD, UreE, UreF, and UreG, which mediate the insertion of nickel into the enzyme active site.