The double face of nickel, being both a toxic element for living organisms and a necessary metal for enzymatic reactions, forces nickel-dependent organisms to develop regulatory networks in order to tightly control the intracellular Ni(II) ion quota, avoiding the occurrence of a free Ni(II) pool and overcoming the natural scarcity of this metal ion in the environment. Among nickel-dependent enzymes, urease is an important virulence factor, being required by pathogens for host colonization and virulence.

Regulation of urease activity by bacteria occurs at different levels, such as transcription, maturation and a catalysis. The regulatory networks controlling urease production and activity rely on intrinsically disordered proteins or regions. Different degrees of protein flexibility of Ni(II)-sensors influence their interactions with DNA, as well as modulate the protein-protein interactions for urease activation and the accessibility of the substrate for the catalytic activity. This chapter focuses on the molecular basis of the conformational changes and interactions based on the structural (and unstructural) information available. Understanding the role of intrinsic disorder for these regulatory networks might be the first step to design possible antimicrobial strategies aimed at identifying new selective drugs for bacterial eradication.

镍的双面既是活生物体的有毒元素，也是酶促反应所必需的金属，它迫使依赖镍的生物体形成调节网络，以紧密控制细胞内Ni（II）离子的配额，从而避免了镍的出现。游离的Ni（II）池并克服了该金属离子在环境中的天然稀缺性。在镍依赖性酶中，脲酶是重要的毒力因子，病原体对于宿主定殖和毒力是必需的。

细菌对脲酶活性的调节发生在不同的水平，例如转录，成熟和催化作用。控制脲酶产生和活性的调节网络依赖于内在无序的蛋白质或区域。Ni（II）传感器的不同程度的蛋白质柔韧性会影响它们与DNA的相互作用，并调节蛋白质与蛋白质之间的相互作用以激活脲酶，并调节底物对催化活性的可及性。本章重点介绍基于结构（和非结构）信息的构象变化和相互作用的分子基础。了解内在失调对于这些调节网络的作用可能是设计可能的抗菌策略的第一步，这些策略旨在确定用于细菌根除的新选择性药物。