Comparative modelling and virtual screening of atypical (RIO) protein kinases from Haemonchus contortus - promise as new targets for nematocidal drugs
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Almost nothing is known about atypical kinases in multicellular organisms, including parasites. We have analysed three RIO kinase genes, riok-1, riok-2 and riok-3, and their products from Haemonchus contortus, one of the most important parasitic nematodes of small ruminants. Based on comparative modelling using the known structures of RIOK-1 and RIOK-2 from Archaeoglobus fulgidus [1,2], the structural comparison of the three RIOKs shows that the RIOK domain harbouring the catalytic site is a wellconserved fold among parasitic nematodes, in particular between H. contortus and T. vitrinus. In a first attempt to probe the active site of RIOKs, with a view toward drug discovery, we conducted an in silico screen with the program LIDAEUS using the homology model of Hc-RIOK-1 and employing the SPECS database. Our findings indicate opportunities for the design of a novel class of nematodespecific inhibitors of RIO kinases. The latter aspect is of paramount importance, given the serious problems linked to anthelmintic resistance in parasitic nematode populations of livestock.
36th Lorne Conference on Protein Structure and Function 2011. Proceedings
Structural Biology (incl. Macromolecular Modelling)