Malaria is one of the deadliest infectious diseases, affecting millions of lives annually and is caused by parasitic protozoans of the genus Plasmodium. P. falciparum (Pf) adopts various survival strategies including post-translational modifications (PTMs) to stabilize and potentiate its crucial proteins for successful infection cycle in the mosquito and human host. One of the important PTMs is called sumoylation, which is essential for normal cellular functions. It is known that SUMO interacts with both E1-activating (hetero-dimeric Aos1/Uba2), and E2-conjugating (Ubc9) individually. Can the interaction of Pf-SUMO with E1and/or E2 have the cross-species interaction element that can be targeted? Moreover, the structure of Pf-SUMO is not known, we present the first structure of Pf-SUMO solved using solution state NMR. The residue specific interactions of Pf-SUMO with Pf-Ubc9 and the possibilities of cross-interaction of host and parasite sumoylation machineries were also checked by NMR titration studies. We have identified the important residues of Pf-SUMO proteins involved in sumoylation that governs the specificity of interaction in Plasmodium as well as human host. The residues at the interacting interface that displayed prominent interactions have been mutated to probe their specificity. Overall, all these results emphasize that during disease condition the parasite may use the host sumoylation machinery to maintain its survival. This information can be used for designing drugs that specifically block the interface. The dynamics of Pf-SUMO protein will also help in ascertaining role of protein plasticity in substrate recognition and specificity.