Nickel is both a toxic and an essential element for microorganisms, including human pathogens, that rely on the activity of urease for survival. The enzymatic activity of urease depends on the chemistry of Ni(II). Urease activation relies on the action of proteins that effect nickel-dependent gene expression (NikR), nickel trafficking (UreE), and GTP hydrolysis (UreG). Recent insights in the structure and function of all these proteins will be illustrated and discussed. The NMR approach to establish structure and dynamics of NikR in solution, and the crystallographic evidence for the importance of disorder in the role of UreE as a metallo-chaperone will be discussed. The properties of UreG as an intrinsically disordered enzyme will be discussed as possible challenges to the structure-function paradigm in enzymology. The crystal structure of urease inhibited with citrate, a competitive inhibitor, will be described, and the potential for structure-based design of new drugs will be considered.

Chemistry of nickel in urease: Novel structural insights from NMR and X-ray crystallography

243rd National Meeting (2012)

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