Chemistry of Ni2+ in urease: sensing, trafficking, and catalysis.

Title	Chemistry of Ni2+ in urease: sensing, trafficking, and catalysis.
Authors	Stefano Benini, Francesco Musiani, Barbara Zambelli, Stefano Ciurli
Magazine	Accounts of Chemical Research
Date	07/19/2011
DOI	10.1021/ar200041k
Introduction	Transition metals play vital roles in enzymatic catalysis yet are scarce in nature. Organisms have evolved mechanisms to selectively sense and utilise metal ions. Changes in metal ion concentrations trigger cellular responses, regulating metal ion homeostasis and enzyme activation. The toxicity of many metal ions necessitates regulated intracellular trafficking, managed by specific chaperones. The Ni(2+)-dependent urease system exemplifies cellular strategies for handling essential but toxic metal ions. Since urease was first identified as nickel-dependent in 1975, the rationale behind Ni(2+) selection and the cascade of metal-dependent gene regulation events leading to enzyme activation remain partially understood. Recent advancements have shed light on Ni(2+)'s role in catalysis and its interaction with Zn(2+) and Fe(2+). This research focuses on structural insights into enzyme interactions with inhibitors and substrate analogues, enhancing understanding of the catalytic mechanism. Structural and functional data clarify Ni(2+) sensing by NikR, a nickel-dependent transcription factor. The urease activation process, involving Ni(2+) insertion into the active site, has been partly analysed through accessory proteins UreD, UreF, and UreG. The intracellular trafficking of Ni(2+) is better understood through the structural properties of metallo-chaperone UreE. Key concepts include Zn(2+)'s role in nickel metabolism, the disordered nature of the GTPase for urease activation, and the regulatory role of accessory proteins.
Quote	Stefano Benini, Francesco Musiani and Barbara Zambelli et al. Chemistry of Ni2+ in urease: sensing, trafficking, and catalysis. 2011. DOI: 10.1021/ar200041k
Element	Nickel (Ni) , Zinc (Zn)
Materials	Chemical Compounds
Industry	Research & Laboratory