The rapid development by malaria parasites of resistance to almost all the chemotherapeutic agents so far used for their control
means that constant efforts to develop new drugs are necessary. In this review, we propose that the exploration of protein-protein interactions
as a new strategy to identify antimalarial drug targets is an attractive and a promising area of research. Nevertheless, one of the most
important criteria is that the targeted gene should encode an essential protein within a complex that is able to affect parasite survival.
Recently, our research on the biology of Plasmodium falciparum allowed us to identify the interaction of Protein Phosphatase type 1 and
actin with two essential partners, PfLRR1 and PfLRR7 respectively, both of which belong to the Leucine Rich Repeat (LRR) protein
family. LRR-containing proteins are composed of several consensus LRR motifs LXLXXNXL (where X is any amino acid) that provide
sites for the assembly of protein interactions. The LRR combines structural versatility, adaptability and more importantly a high degree of
interaction specificity. In addition, it has been shown that a single mutation in a particular LRR motif abolishes the protein-protein interaction
and contributes to the expression of severe pathology in humans. This clearly infers that blocking the interaction related to ‘hot
spots’ of LRR motifs can be considered as good targets to block parasite growth and development. Thus, the inhibition of protein-protein
interactions by peptides, peptidomimetics or small-molecule inhibitors that interfere with binding domains can contribute to defining new
potential drug targets.
Keywords: Plasmodium, protein-protein interactions, LRR protein family, peptidomimetics, drug target, targeted gene, essential protein, Protein Phosphatase type 1, amino acid, mutation
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