Thermodynamics of the Ga³⁺/ Fe³⁺ Competition in a Model of the Heme B-Containing Bacterial Catalase Active Center

Antibiotic resistance presents an enormous threat to human well-being due to the overconsumption and misuse of these essential drugs in recent years. A novel and intriguing path to overcoming the ever-pressing problem appears in the "Trojan horse" strategy exploiting bacteria's internalization systems and their exceptional capability to scavenge metal ions, iron in particular, from the surrounding media when evading the host organism. A promising candidate in this field is the abiogenic cation gallium─a ferric mimetic species, known to exert diverse effects, with its well-pronounced antibacterial activity attracting the attention of scientists in the past decade. In the study presented herewith, the computational chemistry methods, based on Density Functional Theory (DFT), are utilized in order to differentiate those outer factors contributing to gallium's ability to substitute the native ferric ion in the active site of the enzyme catalase. The characteristics of the surrounding media such as pH and solvent exposure, the composition of the protein shell, the nature of the metal, and different substrate molecules have been taken into account. The obtained results are interpreted in light of the experimentally reported observations and aim to contribute to deciphering this aspect of gallium's mechanism of antibacterial activity.