Molecular Details of Urease Inhibition by Boric Acid:  Insights into the Catalytic Mechanism

• Published in: Journal of the American Chemical Society Vol. 126; no. 12; pp. 3714 - 3715
• Main Authors: Benini, Stefano, Rypniewski, Wojciech R, Wilson, Keith S, Mangani, Stefano, Ciurli, Stefano
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 31.03.2004
• Subjects: Binding Sites; Biological and medical sciences; Boric Acids - chemistry; Boric Acids - pharmacology; Enterobacter aerogenes - enzymology; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Hydrogen Bonding; Mechanisms. Catalysis. Electron transfer. Models; Molecular biophysics; Molecular Structure; Physical chemistry in biology; Proteus mirabilis - enzymology; Urease - antagonists & inhibitors; Urease - chemistry; MO method; Frontier orbital; Enzyme; Reaction path; Theoretical study; Enzyme inhibitor; Urease; Metalloenzyme; Boric acid; Binding capacity; Hydrolases; Molecular complex; Catalyst activity
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja049618p

The structure of the complex of urease, a Ni-containing metalloenzyme, with boric acid was determined at 2.10 Å resolution. The complex shows the unprecedented binding mode of the competitive inhibitor to the dinuclear metal center, with the B(OH)3 molecule bridging the Ni ions and leaving in place the bridging hydroxide. Boric acid can be considered a substrate analogue of urea, and the structure supports the proposal that the Ni-bridging hydroxide acts as the nucleophile in the enzymatic process of urea hydrolysis.