Phosphatase Subfamily PFKFB

Phosphatase Classification: Fold HP: Superfamily HP (histidine phosphatase): HP, branch1 family: Subfamily PFKFB

PFKFB is a dual kinase and phosphatase that both phosphorylates and dephosphorylates fructose to fructose 2,6-bisphosphate (Fru-2,6-P2). Fru-2,6-P2 is an allosteric activator of the key glycolysis enzyme phosphofructokinase 1 (Pfk1), so PKFKB activities both activate and deactivate glycolysis.

Evolution

PFKFB is found in most eukaryotic groups, and is thought to result from an early fusion of it's two enzymatic domains (6-phosphofructo-2-kinase (PFK-2) and fructose-2,6-bisphosphatase (FBPase-2). Two distinct genes encoding PFK-2 and FBPase-2, or related enzymes with broader substrate specificity, fused resulting in a bifunctional enzyme both domains of which had, or later acquired, specificity for fructose 2,6-bisphosphate [1, 2].

This enzyme is duplicated in many lineages, sometimes losing either kinase or phosphatase activity in the duplicates, and in some parasitic lineages, the gene is lost entirely [2]

Domain

PFKFB has two domains for its two functions [1, 2]:

• The kinase PFK-2 domain for synthesis of Fru-2,6-P2, has an adenylate kinase fold, confirmed by crystal structure.
• The phosphatase FBPase-2 domain for degradation of Fru-2,6-P2 is a HP1 domain.

Functions

PFKFB is a homodimeric bifunctional enzyme that catalyses both the synthesis and degradation of Fru-2,6-P2 (fructose 2,6-bisphosphate) during glycolysis [1, 2]. Fru-2,6-P2 is also the substrate of Subfamily TIGAR, another subfamily of HP1 phosphatases. The four human PFKFBs have slightly different gene expression across different tissues. PFKFB3 has an isoform-specific S-glutathionylation, which mediates its functions in regulating oxidative stress homeostasis [3].

References

Error fetching PMID 15170386:
Error fetching PMID 24295899:
Error fetching PMID 16766380: