Abstract
Phosphoglycerate kinase (PGK) is a glycolytic enzyme that is well conserved among the three domains of life. PGK is usually a monomeric enzyme of about 45 kDa that catalyses one of the two ATP-producing reactions in the glycolytic pathway, through the conversion of 1,3-bisphosphoglycerate (1,3BPGA) to 3-phosphoglycerate (3PGA). It also participates in gluconeogenesis, catalysing the opposite reaction to produce 1,3BPGA and ADP. Like most other glycolytic enzymes, PGK has also been catalogued as a moonlighting protein, due to its involvement in different functions not associated with energy metabolism, which include pathogenesis, interaction with nucleic acids, tumorigenesis progression, cell death and viral replication. In this review, we have highlighted the overall aspects of this enzyme, such as its structure, reaction kinetics, activity regulation and possible moonlighting functions in different protistan organisms, especially both free-living and parasitic Kinetoplastea. Our analysis of the genomes of different kinetoplastids revealed the presence of open-reading frames (ORFs) for multiple PGK isoforms in several species. Some of these ORFs code for unusually large PGKs. The products appear to contain additional structural domains fused to the PGK domain. A striking aspect is that some of these PGK isoforms are predicted to be catalytically inactive enzymes or ‘dead’ enzymes. The roles of PGKs in kinetoplastid parasites are analysed, and the apparent significance of the PGK gene duplication that gave rise to the different isoforms and their expression in Trypanosoma cruzi is discussed.
Highlights
Metabolism is a fundamental process in living organisms, consisting of a network of biochemical reactions catalysed and regulated by enzymes
A possible explanation previously proposed for the presence of this flagellar degenerated Phosphoglycerate kinase (PGK) enzyme in T. brucei is a change to glycolysis regulation and compartmentalization during kinetoplastid evolution [60], we suggest that it may rather be related with a protein that acts as a ‘functionally flexible’ enzyme, fulfilling different cellular tasks not related to the proper PGK function, but adapted to the environmental and nutritional requirements of the different groups of kinetoplastids
When analysing the genomes of different kinetoplastid species, we found several important data about this glycolytic/ gluconeogenic enzyme. (i) The number of genes encoding PGK isoenzymes and PGK-related proteins (‘dead’ PGKs) can vary greatly in these protists, from 1 to 6. (ii) Some of these PGKs have additional domains such as a PAS, cyclic nucleotide binding domains (CNB) and/or some transmembrane regions of which the location within the overall protein structure may vary
Summary
Metabolism is a fundamental process in living organisms, consisting of a network of biochemical reactions catalysed and regulated by enzymes The activities of these enzymes support a wide variety of processes such as cell growth and proliferation, synthesis of cellular components and generation of forms of energy to sustain them. The significant presence of PKs encoded in these parasites suggests a key role of these enzymes in their biology [4] These parasites belong to the Kinetoplastea, a group of flagellated protists comprising members that parasitize many plant and animal species, and in humans are responsible for diseases with serious public health threats and socioeconomic effects [5].
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