Molecular details of urease inhibition by boric acid: insights into the catalytic mechanism.
The structure of the complex of urease, a Ni-containing metalloenzyme, with boric acid was determined at 2.10 A 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.
Benini
Stefano
S
York Structural Biology Laboratory, University of York, York, UK.
Rypniewski
Wojciech R
WR
Wilson
Keith S
KS
Mangani
Stefano
S
Ciurli
Stefano
S
D001665:Binding Sites; D001888:Boric Acids / Q000737:chemistry / Q000494:pharmacology*; D021902:Enterobacter aerogenes / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D015394:Molecular Structure; D011513:Proteus mirabilis / Q000201:enzymology; D014510:Urease / Q000037:antagonists & inhibitors* / Q000737:chemistry
D001888:Boric Acids; D004791:Enzyme Inhibitors; D014510:Urease; C032688:boric acid