Academic Journal
Chemistry of Ni2+ in urease: sensing, trafficking, and catalysis.
| Τίτλος: | Chemistry of Ni2+ in urease: sensing, trafficking, and catalysis. |
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| Συγγραφείς: | Zambelli B; Laboratory of Bioinorganic Chemistry, University of Bologna, Italy., Musiani F, Benini S, Ciurli S |
| Πηγή: | Accounts of chemical research [Acc Chem Res] 2011 Jul 19; Vol. 44 (7), pp. 520-30. Date of Electronic Publication: 2011 May 04. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 0157313 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4898 (Electronic) Linking ISSN: 00014842 NLM ISO Abbreviation: Acc Chem Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, American Chemical Society. |
| Ιατρικοί όροι (MeSH): | Nickel/*chemistry , Urease/*metabolism, Bacillus/enzymology ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Canavalia/enzymology ; Carrier Proteins/chemistry ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Enterobacter aerogenes/enzymology ; GTP Phosphohydrolases/metabolism ; Helicobacter pylori/enzymology ; Ions/chemistry ; Urease/chemistry ; Urease/genetics ; Binding Sites ; Biocatalysis ; Catalytic Domain ; Phosphate-Binding Proteins ; Transcription, Genetic |
| Περίληψη: | Transition metals are both essential to enzymatic catalysis and limited in environmental availability. These two biological facts have together driven organisms to evolve mechanisms for selective metal ion sensing and utilization. Changes in metal ion concentrations are perceived by metal-dependent transcription factors and transduced into appropriate cellular responses, which regulate the machineries of competitive metal ion homeostasis and metallo-enzyme activation. The intrinsic toxicity of the majority of metal ions further creates a need for regulated intracellular trafficking, which is carried out by specific chaperones. The Ni(2+)-dependent urease enzymatic system serves as a paradigm for studying the strategies that cells use to handle an essential, yet toxic, metal ion. Although the discovery of urease as the first biological system for which nickel is essential for activity dates to 1975, the rationale for Ni(2+) selection, as well as the cascade of events involving metal-dependent gene regulation and protein-protein interactions leading to enzyme activation, have yet to be fully unraveled. The past 14 years since the Account by Hausinger and co-workers (Karplus, P. A.; Pearson, M. A.; Hausinger, R. P. Acc. Chem. Res. 1997, 30, 330-337) have witnessed impressive achievements in the understanding of the biological chemistry of Ni(2+) in the urease system. In our Account, we discuss more recent advances in the comprehension of the specific role of Ni(2+) in the catalysis and the interplay between Ni(2+) and other metal ions, such as Zn(2+) and Fe(2+), in the metal-dependent enzyme activity. Our discussion focuses on work carried out in our laboratory. In particular, the structural features of the enzyme bound to inhibitors, substrate analogues, and transition state or intermediate analogues have shed light on the catalytic mechanism. Structural and functional information has been correlated to understand the Ni(2+) sensing effected by NikR, a nickel-dependent transcription factor. The urease activation process, involving insertion of Ni(2+) into the urease active site, has been in part dissected and analyzed through the investigation of the molecular properties of the accessory proteins UreD, UreF, and UreG. The intracellular trafficking of Ni(2+) has been rationalized through a deeper understanding of the structural and metal-binding properties of the metallo-chaperone UreE. All the while, a number of key general concepts have been revealed and developed. These include an understanding of (i) the overall ancillary role of Zn(2+) in nickel metabolism, (ii) the intrinsically disordered nature of the GTPase responsible for coupling the energy consumption to the carbon dioxide requirement for the urease activation process, and (iii) the role of the accessory proteins regulating this GTPase activity. |
| Substance Nomenclature: | 0 (Bacterial Proteins) 0 (Carrier Proteins) 0 (Ions) 0 (Phosphate-Binding Proteins) 0 (UreD protein, Bacteria) 0 (UreE protein, Bacteria) 0 (UreF protein, bacteria) 0 (ureG protein, Bacteria) 7OV03QG267 (Nickel) EC 3.5.1.5 (Urease) EC 3.6.1.- (GTP Phosphohydrolases) |
| Entry Date(s): | Date Created: 20110506 Date Completed: 20111122 Latest Revision: 20240109 |
| Update Code: | 20260130 |
| DOI: | 10.1021/ar200041k |
| PMID: | 21542631 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1520-4898 |
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| DOI: | 10.1021/ar200041k |