Manganese is a crucial element for a variety of organisms. Its primary functions include serving as a cofactor for essential enzymes and providing protection against oxidative stress.1-3 The manganese present in human body is the source of this metal ion for pathogenic bacteria, where its presence is directly linked to the bacterial virulence and defense against host-induced oxidative stress. To prevent bacterial infections, the host prevents the acquisition of essential nutrients by pathogens using various methods, one of them being nutritional immunity. In this strategy metal ions, such as Fe(II), Mn(II) and Zn(II), are chelated from the site of infection by specialized extracellular chelator proteins known as the S100 family.4 One member of this family – calprotectin possesses an unique Mn(II) binding site, consisting of six histidine residues, and no oxygen donors. The hexahistidine Mn(II) binding site is unusual as the presence of oxygen donors is consistent with Mn(II) being classified as a hard acid.5,6
The studies of the peptidic fragments of proteins with transition metal ions could help us understand the factors that drive the complexation process, especially in the case of metals with poorly known coordination chemistry in relation to peptide ligands, such as Mn(II) and Fe(II) ions.7,8 Here, we report our latest findings on thermodynamic studies of Mn(II), Fe(II), and Zn(II) complexes using calprotectin fragments involved in metal ions binding, and their mutants. The studies aim to identify which of the present histidine residues are crucial for metal ion binding, and to assess how the mutations of subsequent histidines affect the thermodynamic stability of the studied metal complexes.
The project leading to these results has received funding from the National Science Centre Poland, UMO-2021/43/D/ST4/01231