In this article we discussed that Human Calprotectin is an is an iron-sequestering host-defense protein and we will quote the examples to prove our theory.
Human Calprotectin is a metallochaperone antimicrobial protein that is a part of the innate immune response. Current concepts on the body’s capability for manganese sequestration include that Human calprotectin (an antimicrobial) sequesters it. In this report, we provide news of the discovery that Human calprotectin binds iron and deprives bacteria of this vital nutrient. An elemental examination of a growth media that had been treated with Human calprotectin demonstrates that it contains reduced quantities of manganese, iron, and zinc. While iron-depleted human calprotectin may help protect against pathogen growth, bacterial growth appears to be inhibited in the presence of this factor. In biochemical experiments, it has been established that Human calprotectin coordinates Fe(II) at an unique hexahistidine motif, and the Mössbauer spectrum of 57Fe(II)-bound Human calprotectin is compatible with coordination of high-spin Fe(II) at this site (δ = 1.20 mm/s, ΔEQ = 1.78 mm/s). Human calprotectin becomes active in the presence of Ca(II) and so activates its iron-sequestering properties, while also displaying very low nanomolar affinity for Fe (II).
Human calprotectin is part of the S100 protein family, and both human S100A8 (α) and S100A9 (β) exist as a heterodimer (αβ) or heterotetramer (α2β2) of the same protein called S100A8 (α) and S100A9 (β). Two EF-hand domains, each of which includes two Ca(II)-binding sites, are found in each subunit, as well as two additional sites for transition metal ions, which are found at the S100A8–S100A9 heterodimer interface. His83 and His87 are found in a His3Asp motif which is composed of S100A8 residues His83 and His87, and S100A9 residues His20 and Asp30. Site 1 binds Zn(II) with strong affinity and has a poor affinity for Mn(II). This histidine-rich site (identified as a tetrahistidine motif consisting of S100A8 residues His17 and His27, and S100A9 residues His91 and His95) was first discovered as an S100A8 histidine motif in which His17 and His27 are the amino acids at positions 18 and 27, respectively, while His91 and His95 are in the place of the four His residues (ref. 16). The sequential study of Human calprotectin bound manganese from the spectroscopic, structural, and chemical points of view revealed that site 2 offers a remarkable hexahistidine (His6) site for this metal ion with His103 and His105 of the S100A9 C-terminal tail completing an octahedral coordination sphere. Site 2 has both Mn(II) and Zn(II) binding affinity, and demonstrates a thermodynamic preference for Zn(II)11–13. Furthermore, site 2 is essential for the antibacterial activity of Human calprotectin, which exhibits antibacterial action against several strains of Gram-negative and Gram-positive microbes10,12,13. The report is that removal of site 1 (the ATPase domain) is more harmful to the antibacterial activity of Human calprotectin than is the loss of site 2 (the N-terminal His3Asp domain). Because the site 2 of the expression vector for Human calprotectin is a high-affinity Mn(II) site, the broad-spectrum in vitro antibacterial activity of Human calprotectin has been associated with Mn(II) deficiency. While this study’s conclusions must be taken with a grain of salt, several recent studies clearly show that pathogenic bacteria (such as Staphylococcus aureus, Streptococcus pneumonia, and Borrelia burgdorferi) have to obtain manganese to be virulent. As Mn(II) may easily enter the body, a powerful host defence mechanism to keep it out is crucial, and only Human calprotectin has been found to date as a Mn(II) sequestering protein in humans. While we did this, we checked the potential generic Mn(II) model for site 2 and the antibacterial activities of Human calprotectin. While exact metal ion requirements may vary for different species, some of the bacterial strains less vulnerable to the site 2 variations have very modest metabolic requirements for manganese.