Antifungal activities of lactoferrin peptides: Crystal structural studies of complexes formed between fungal protease proteinase K and lactoferrin/designed peptides.

Department of Biophysics,, All India Institute of Medical Sciences, New Delhi.
○R. Prem kumar Amit kumar Singh Nagendra Singh Sujata Sharma Asha Bhushan Punit Kaur T. P. Singh

Proteins of the transferrin family fulfil a key role in controlling the levels of free iron in the body fluids of animals. Lactoferrin is a prominent member of the transferrin family. In addition to sequestering iron it has several other functions including presence of surface peptides with antibacterial and antifungal properties. Several complexes of proteinase K with proteolytic products of lactoferrin as well as with designed peptides were crystallized using hanging drop method. The lactoferrin peptides included GDEQGENK, VLLH, LLFND and KLKLLVVIRLK. Similarly a number of peptides containing sequences assumed to be having antifungal properties in lactoferrin were synthesized and their complexes with proteinase K were also crystallized. Crystal structures of these complexes were determined and positions of peptide atoms were refined. The structures have revealed that most of the peptides were located in the region between seqments 100-105 and 131-136. The peptides were stabilized by several backbone hydrogen bonds and hydrophobic interactions with residues of ligand binding region. The prominent interactions included His 69, Gly 100, Gly 134 and Ser 224.