Figure 1.

Side (A,B) and top (C,D) views of the crystal structures of diferric human lactoferrin (hLf) (A,C) (PDB code = 1B0L) and bovine lactoferrin (bLf) (B,D) (PDB code = 1BLF). The N-lobe is highlighted in orange and the C-lobe in cyan, the connecting α-helix (aa. 334–344 for both glycoproteins) in violet, and the ferric irons are depicted as black spheres. The lactoferricin (aa. 1–47 in hLf and 17–41 in bLf) and lactoferrampin (aa. 269–285 in hLf and 268–284 in bLf) regions are highlighted in blue and green, respectively. N-terminal regions, able to interact with different glycosaminoglycans on cancer cells, are depicted in red and correspond to the first five amino acids (G¹RRRR⁵) for hLf, while in bLf only Asn in position 5 (N⁵) is shown, as the first four amino acids (A¹PRK) are absent in the crystal structure. As evident from the top view, the cationic lactoferricin, lactoferrampin and the N-terminal region are packed close to each other and constitute a basic domain able to interact with prokaryotic and eukaryotic cell surface receptors, thus exerting multifaceted activities.