Send to

Choose Destination
J Mol Graph Model. 2009 Feb;27(6):665-75. doi: 10.1016/j.jmgm.2008.10.009. Epub 2008 Nov 6.

Comparative modeling of thioredoxin glutathione reductase from Schistosoma mansoni: a multifunctional target for antischistosomal therapy.

Author information

Center for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology (IIIT-H), Gachibowli, Hyderabad 500032, India.

Erratum in

  • J Mol Graph Model. 2010 Nov;29(3):506.


Schistosoma mansoni, a trematode parasite, which causes schistosomiasis and affects more than 200 million people worldwide, lives in an aerobic environment and therefore needs an effective redox mechanism for surviving reactive oxygen species from its host. Although, the host has two different redox systems: glutaredoxin and thioredoxin, the parasite has only one unique multifunctional enzyme, thioredoxin glutathione reductase (TGR) involving a fusion of two proteins, glutaredoxin (Grx) and thioredoxin reductase (TR), for performing all the redox activities. This dependence of S. mansoni on a single protein, TGR, for its protection from oxidative stress, makes it a promising drug target. Here, we describe a suitably validated, homology model for S. mansoni TGR (SmTGR), developed using both TR and Grx templates, functionally complete in the dimeric form with cofactors NADP(H) and FAD. Comparative analysis of substrate and inhibitor binding pockets of our model with crystal structures of parent TR as well as with that of glutathione reductase (GR), which is an essential component of the Grx system, appears to provide greater insight into the functioning of TGR. This also augments recent observations reported on the basis of X-ray structure data on SmTGR monomer lacking the C-terminal selenocysteine tail.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center