Other potentially significant protease associated networks Proteases in P. falciparum may perhaps play other roles impor tant for parasite biology. We previously identified a sin gle copy of calpain PfCalp in P. falciparum genome. Calpain is important for signal transduction, cell cycle regulation, differentiation, development, and cell cell communication from bacteria to humans. Extremely tiny is identified about its part in P. falci parum. Only 4 proteins seemed to be related with calpain which includes a putative protein with a C3HC4 sort zinc finger, the motif commonly present in transcrip tional regulators, a ribosomal protein, and two proteins with unknown function. Even so, partial knockdown assays not too long ago suggested that PfCalp is crucial for the parasites optimal development and cell cycle progression.
Phylogenetic evaluation revealed that PfCalp is a unique sort of calpain confined to alveolates with distant relatedness to human calpains, adding it to a
of promising drug tar get. Yet another class of proteases that mediate cell cycle regulation and programmed cell death is comprised on the three metacaspases in the C14 protease household. Only selleck chemical MK-2206 one association partner was identified for PF130289 and PF140363. and no associations had been identified for PF140160, reflecting our limited expertise about their functions in malaria parasite. Conclusions Our network analysis of proteases from P. falciparum utilizes a so called guilt by association method to extract sets of proteins in the proteome that happen to be candidates for additional study.
The network biology approach is read ily adapted to any system for which a genome selleck sequence exists and for which some type of protein protein asso ciation is accessible, while you will discover limitations. A few of these stem from missing information, andor noisy data, which cause underestimation of the S value for a pair of associated proteins, but this dilemma becomes less considerable with every release of data. A second problem may be the lack of any dynamic element in evaluating the associations. A much more formal integration of expression data could aid to ameliorate this circumstance, particularly expression data sets gathered beneath unique conditions. In spite of these limitations, our benefits produced identified associations, which serve as positive controls which include the ubiquitin proteasome technique.
Additionally, it indicated that proteases are playing previously unrecognized role in the biology of the parasite, including the proteases that mediate the tension responses. Our benefits also imply that certain of those proteases, which include the proteases that mediate regulated intramembrane proteolysis, parasite egress, and signal peptide processing and protein secre tion, can be superior candidates for antimalarial targeting, as they are extremely connected inside the network. Additional extra, some of these candidates are known to possess no or only distantly connected homologs in humans, which reduces the probability of adverse effects resulting from their inactivation.