Schistosoma mansoni and Plasmodium falciparum are pathogen parasites that spend part of their lives in the blood stream of the human host and are therefore heavily exposed to fluxes of toxic reactive oxygen species (ROS). SmTGR, an essential enzyme of the S. mansoni ROS detoxification machinery, is known to be inhibited by Auranofin although the inhibition mechanism has not been completely clarified. Auranofin also kills P. falciparum, even if its molecular targets are unknown. Here, we used computational and docking techniques to investigate the molecular mechanism of interaction between SmTGR and Auranofin. Furthermore, we took advantage of the homology relationship and of docking studies to assess if PfTR, the SmTGR malaria parasite homologue, can be a putative target for Auranofin. Our findings support a recently hypothesized molecular mechanism of inhibition for SmTGR and suggest that PfTR is indeed a possible and attractive drug target in P. falciparum. © 2011 Elsevier Inc.
|Number of pages
|Biochemical and Biophysical Research Communications
|Published - Jan 2012
Bibliographical noteKAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): KUK-I1-012-43
Acknowledgements: We thank the members of the Fondazione Roma Research Unit led by Prof. Maurizio Brunori for useful discussions and Prof. Arthur Lesk for critically reading the manuscript. This work was partially supported by Award number KUK-I1-012-43 made by King Abdullah University of Science and Technology (KAUST), FIRB Proteomica, Ministery of Health Grant Contract No. Onc_Ord 25/07, Fondazione Roma and the IIT SEED project.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.