Modeled Structure of Trypanothione Synthetase of Leishmania infantum for development of novel therapeutics for leishmaniasis

Trypanothione synthetase (TryS) is an important enzyme for survival of Leishmania; thus an important target for structure based drug design against leishmaniasis. We have constructed three-dimensional structure of the TryS of Leishmania infantum by homology modeling with acceptable Ramachandran statistics. The modeled structure TryS is compared with human (host) glutathione synthetase (GS) and Escherichia coli glutathionyspermidine synthase (GspS) involved in similar functions. Remarkable structural difference between human GS and TryS, opens a new avenue to design specific TryS inhibitor drugs against leishmaniasis without interfering GS activity. Interestingly, GS displays very little sequence or structure identity with GspS or TryS. Since there is no success yet in solving the crystal structure of TryS of any species of Leishmania, the current modeled structure will be used for our ongoing docking study to identify potentials inhibitors.