The Evolution Study Of 6-Cysteine Family Member Protein of Plasmodium sp. As a Potential Drug Candidate Against Malaria Infection
Abstract
The increase of current antimalarial drug resistance was reported and lead to the greatest threats to malaria control; therefore, new methods should be applied to encounter this problem. Although the protein evolution study of Plasmodium may contain valuable information in finding a new antimalarial drug candidate, the cross-species antimalaria drug cannot be made because there is no sufficient information regarding the protein evolution between human-infecting and non- infectious Plasmodium. In this study, data mining from PlasmoDB discovers several proteins shared by Plasmodium where some of them include in a 6-Cysteine protein family. Previous studies revealed that 3 of 6-Cysteine family members (P41, P48/45, and P230) could be used as a vaccine candidate. From this information, the evolution properties and the characteristics of these proteins were further analyzed. Protein sequences of 6-Cysteine protein family members were retrieved from plasmoDB and the GenBank. Maximum likelihood phylogenetic tree and time trees were then constructed by using MEGAX, protein domain analysis was done by using InterPro, and all tertiary structures of these proteins were predicted by using PHYRE2. Phylogenetic tree and time tree analysis showed that the human-infecting and the non-infectious Plasmodium have a different cluster and evolutionary rates. Furthermore, several domains that can be used vaccine targets were found in P41, P48/45, and P230, such as transmembrane, signal peptide, and a coiled-coil domain. Tertiary structure prediction also revealed a different characteristic of these proteins. Thus, our findings provide valuable information to support the development of the cross-species antimalaria vaccine using 6-Cysteine protein family members.
Keywords: 6-Cysteine, drug target, protein domain, protein evolution, tertiary structure, Plasmodium
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