Structural and evolutionary characteristics of pyruvate phosphate dikinase in Giardia lamblia and other amitochondriate protozoa.

BACKGROUND

Pyruvate phosphate dikinase (PPDK) reversibly catalyzes the interconversion of phosphoenolpyruvate (PEP) and pyruvic acid, leading to catabolism and adenosine triphosphate (ATP) synthesis or gluconeogenesis and ATP consumption. Molecular modeling of PPDKs from divergent organisms demonstrates that the orientation of the phosphorylatable histidine residue within the central domain of PPDK determines whether this enzyme promotes catabolism or gluconeogenesis. The goal of this study was to determine whether PDDK from Giardia underwent adaptive evolution in order to produce more energy under anaerobic conditions.

METHODS

A total of 123 PPDK sequences from protozoans, proteobacteria, plants, and algae were selected, based upon sequence similarities to Giardia lamblia PPDK and Zea mays PPDK. Three-dimensional (3-D) models were generated for PPDKs from divergent organisms and were used to compare the orientation of the phosphorylatable histidine residue within the central domain of PPDKs. These PPDKs were compared using a maximum-likelihood tree.

RESULTS

For PPDK from Giardia, as well as from other anaerobic protozoans, the central domain tilted toward the N-terminal nucleotide-binding domain, indicating that this enzyme catalyzed ATP synthesis. Furthermore, the orientation of this central domain was determined by interactions between the N- and C-terminal domains. Phylogenetic analysis of the N- and C-terminal sequences of PPDKs from different species suggested that PPDK has likely undergone adaptive evolution in response to differences in environmental and metabolic conditions.

CONCLUSIONS

These results suggested that PPDK in anaerobic organisms is functionally adapted to generate energy more efficiently in an anaerobic environment.