Plasmodium vivax malaria is a globally widespread disease responsible for 50% of 
human malaria cases in Central and South America, South East Asia and Indian 
subcontinent. The rising severity of the disease and emerging resistance of the 
parasite has emphasized the need for the search of novel therapeutic targets to 
combat P. vivax malaria. Plasmepsin 4 (PM4) a food vacuole aspartic protease is 
essential in parasite functions and viability such as initiating hemoglobin 
digestion and processing of proteins and is being looked upon as potential drug 
target. Although the plasmepsins of Plasmodium falciparum have been extensively 
studied, the plasmepsins of P. vivax are not well characterized. This is the 
first report detailing complete PM4 gene analysis from Indian P. vivax isolates. 
Blast results of sequences of P. vivax plasmepsin 4 (PvPM4) shows 100% homology 
among isolates of P. vivax collected from different geographical regions of 
India. All of the seven Indian isolates did not contain intron within the coding 
region. Interestingly, PvPM4 sequence analysis showed a very high degree of 
homology with all other sequences of Plasmodium species available in the 
genebank. Our results strongly suggest that PvPM4 are highly conserved except a 
small number of amino acid substitutions that did not modify key motifs at 
active site formation for the function or the structure of the enzymes. 
Furthermore, our study shows that PvPM4 occupies unique phylogenetic status 
within Plasmodium group and sufficiently differ from the most closely related 
human aspartic protease, cathepsin D. The analysis of 3D model of PM4 showed a 
typical aspartic protease structure with bi-lobed, compact and distinct peptide 
binding cleft in both P. vivax and P. falciparum. In order to validate 
appropriate use of PM4 as potential anti-malarial drug target, studies on 
genetic and structural variations among P. vivax plasmepsins (PvPMs) from 
different geographical regions are of utmost importance for drugs and vaccine 
designs for anti-malarial strategies.