Studies on ornithine decarboxylase of Leishmania donovani: structure modeling and inhibitor docking

Abstract

Leishmaniasis is a detrimental disease caused by the parasite Leishmania which has a unique redox metabolism involving trypanothione. Trypanothione delivers reducing equivalents which in turn saves the parasite from oxidative damage and is also utilized in the formation of deoxyribonucleotides. The polyamine biosynthesis pathway starts with the conversion of ornithine to spermidine, precursor of trypanothione, by ornithine decarboxylase. Thus, targeting ornithine decarboxylase would inhibit formation of spermidine and subsequently trypanothione, affecting the growth and survival of Leishmania. This enzyme could be a good drug target to combat leishmaniasis. In the current study, we have predicted the 3D structure of Leishmania donovani ornithine decarboxylase. Moreover, we have conducted structure-based virtual screening against the enzyme in an attempt to find potential leishmania-specific inhibitors. Interactions of the leishmanial enzyme with the inhibitors have also been investigated to identify functionally important residues.