Intrinsic disorder in the nickel-dependent urease network

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.