3-PGK

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Introductions

Phosphoglycerate kinase PGK is a key enzyme in glycolysis and is essential for the survival of every organism. PGK is a monomeric, highly flexible glycolytic enzyme that consists of two spherical structural thresholds that undergo significant conformational changes during substrate binding and ultimately catalytic effects. This enzyme is found in only one type in some bacterial cells, while in most organisms it contains two to three isozymes. PGK is present in all organic life and its sequence is highly conserved throughout the evolutionary process.

3-phosphoglycerate kinase

The 3-phosphoglycerate kinase catalyzes the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate, producing one molecule of ATP, which is the first production of ATP during anaerobic digestion. since it is 1 molecule of glucose that produces 2 molecules of 1,3-diphosphoglycerate, 1 molecule of glucose can produce 2 molecules of ATP in this process. ATP is produced by horizontal phosphorylation of the substrate, and energy is transferred directly from the high-energy phosphate group in the substrate to ADP to form ATP.

Structure

The PGK has been isolated from a variety of organisms. It is a typical hinge-bending monomeric enzyme with a molecular weight of about 45 kDa. the enzyme consists of a folded polypeptide chain forming two structural domains of almost equal size separated by a deep cleft and joined by two α-helices (α-helices 7 and 14), giving it a unique bilobed structure. both the N-terminal and C-terminal structural domains contain a typical Rothman fold with a core of six parallel β-folded chains surrounded by α-helices. The β corner and irregular structural fragments connect the β fold to the α helix. Both structural domains are involved in substrate binding.

Figure 1. Structure of PGK. (Pirela M, et al. 2020)

Nucleotide regulation

PGK activity is regulated by various nucleotides (AMP, ATP, ADP), as documented in different organisms. the presence of AMP, ADP, GDP, GMP, IDP and IMP inhibits rabbit muscle PGK. apparently, the inhibition is mixed. This purine nucleotide-mediated regulation has also been observed in plants. In pea, cytosolic and chloroplast PGK activity in the direction of ATP production is regulated by AMP and ATP, while in the opposite direction (using ATP), regulation occurs through AMP and ADP. For yeast, there are references to ADP and AMP inhibition of PGK. Apparently, this enzyme has two nucleotide binding sites, a binding site for the substrate ATP/ADP and another ADP regulatory site separate from the nucleotide substrate. AMP is also bound to the enzyme, probably at the same site as the substrate ATP. In addition, ADP is a competitive inhibitor, whereas AMP is a non-competitive 3PGA binding inhibitor. This inhibition mechanism may reflect an interesting way of regulating the direction of the enzyme's reversible reaction.

PGK as a moonlighting protein

Moonlighting proteins contain heterogeneous collections of proteins from different classes that can perform a variety of physiologically relevant biochemical or biophysical functions. Currently, more than 300 moonlighting proteins have been identified. These proteins are expressed throughout the "tree of life" organism and their primary functions are attributed to different biochemical processes. Some of these proteins are able to perform both their primary and secondary functions (moonlighting), while others change their functions depending on the environment. Among the metabolic enzymes, seven glycolytic enzymes have been identified as moonlighting proteins, one of which is PGK. In various organisms, in addition to their canonical functions in glycolysis and gluconeogenesis, other functions in various cellular processes have been attributed to PGK, including a role in parasite-host relationships.

Figure 2. PGK moonlighting functions. (Pirela M, et al. 2020)

Conclusion

PGK is a highly conserved enzyme distributed in archaea, bacteria and eukaryotes. Its main functions are related to carbohydrate metabolism, especially glycolysis and gluconeogenesis, but the enzyme can also be involved in a variety of other biological processes, such as cell invasion, angiogenesis and tumor growth, flagellar motility, viral replication, induction of autophagy, and cell proliferation.