Difference between revisions of "Phosphatase Subfamily PFKFB"
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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]] (histidine phosphatase): [[Phosphatase_Family_HP1|HP, branch1 family]]: [[Phosphatase_Subfamily_PFKFB|Subfamily PFKFB]] | [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]] (histidine phosphatase): [[Phosphatase_Family_HP1|HP, branch1 family]]: [[Phosphatase_Subfamily_PFKFB|Subfamily PFKFB]] | ||
| − | 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 === | === Evolution === | ||
| − | PFKFB | + | 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 <cite>rider04, michel06</cite>. |
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 <cite>michel06</cite> | 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 <cite>michel06</cite> | ||
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=== Functions === | === 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 <cite>rider04, michel06</cite>. Fru-2,6 | + | PFKFB is a homodimeric bifunctional enzyme that catalyses both the synthesis and degradation of Fru-2,6-P2 (fructose 2,6-bisphosphate) during glycolysis <cite>rider04, michel06</cite>. Fru-2,6-P2 is also the substrate of [[Phosphatase_Subfamily_TIGAR|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 <cite>Seo14</cite>. | 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 <cite>Seo14</cite>. | ||
Revision as of 16:51, 15 May 2016
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
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