Plasmodium spp. Enolase: A Housekeeping

Enolases are highly conserved proteins that catalyze the interconversion of 2-phosphoglyceric acid and phosphoenolpyruvate [1]. This is an essential step during glycolysis as well as gluconeogenesis. Interestingly, evolution has incorporated multiple novel non-glycolytic functions in several glycolytic enzymes (Reviewed in [2]). Such non-glycolytic or ‘moonlighting functions’ of enolase range from its role in transcription regulation [3-6], to invasion of host cells [7-10], to structural roles [11]. Enolases from apicomplexan parasites are more similar to plant orthologs as compared to host enolases. A distinct feature of malarial parasite Plasmodium enolase is its diverse distribution inside the cell. Such multi-compartmental localization is indicative of this protein possessing organelle-specific physiological functions. Recent observations have detected the presence of this enzyme in food vacuole [12]; nucleus; cytoskeletal elements ; cell surface of invasive stages sporozoites, merozoites [13] and ookinetes [14] etc. Although the protein doesn’t have any organelle-specific signal sequence [15], yet it finds its diverse destinations in the cell. Structural diversity as evident from the multiple electrophoretic variants [12,16-20] that largely arises due to post-translational modifications (PTMs) is likely to form the molecular basis for its stage-dependent diverse sub-cellular functions. Although the primary sequence of this protein is highly conserved, minor structural alterations have accumulated over the course of evolutionary time scales [21]. A distinct structural feature of Plasmodial enolase is the presence of a five amino acid insert 104EWGWS108 in a surface loop [22]. It is instructive to investigate whether such unique insert elements indeed form the structural basis for parasite specific moonlighting functions. Multiple strategies (NMR, ITC, site-directed mutagenesis, immunological etc.) have been employed to understand its functional significance [23-28].