Competition between Ag+ and Ni2+ in nickel enzymes: Implications for the Ag+ antibacterial activity

Abstract

Silver's antimicrobial properties have been known for centuries, but exactly how it kills bacteria is still a mystery. Information on the competition between the native Ni2+ and abiogenic Ag+ cations in bacterial systems is also critically lacking. For example, urease, a famous nickel-containing enzyme that hydrolyzes urea into carbon dioxide and ammonia (a key step in the biogeochemical nitrogen cycle on Earth), is inhibited by Ag+ cations, but the molecular mechanism of silver’s action is poorly understood. By employing density functional theory (DFT) calculations combined with the polarizable continuum model (PCM) computations we assess the susceptibility of the mono/binuclear Ni2+ binding sites in the nickel enzymatic centers to Ni2+→Ag+ substitution. The active centers in the mononuclear glyoxalase I and acireductone dioxygenase enzymes appear to be well protected against Ag+ attack and, presumably, stay functional even in its presence. On the other hand, the binuclear nickel binding site in urease appears vulnerable to silver attack - the results obtained are in line with available experimental data and give reason to assume a possible substitution of the essential Ni2+ cation from the urease metal center by Ag+.