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On the binding mode of urease active site inhibitors: A density functional study
Author(s) -
Leopoldini M.,
Marino T.,
Russo N.,
Toscano M.
Publication year - 2008
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.21758
Subject(s) - chemistry , nucleophile , active site , boric acid , urease , covalent bond , boron , catalysis , density functional theory , computational chemistry , enzyme , atom (system on chip) , stereochemistry , organic chemistry , computer science , embedded system
The way with which boric acid, a rapid reversible competitive inhibitor, binds the urease active site was explored at density functional B3LYP level of theory. The catalytic core of the enzyme was simulated by two models of different size. In both cases, amino acid residues belonging to the inner and to the outer coordination spheres of nickel ions were replaced by smaller molecular species. Contrary to the experimental indication that attributes the inhibitory ability of this acid to the lack of a nucleophilic attack by the enzyme to the boron atom, we instead found that another possibility exists based on the presence of a strong covalent σ bond between boron and urease that we think can be hardly broken to allow any course of the reaction. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2008