Difference between revisions of "Phosphatase Subfamily PFKFB"
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* The phosphatase FBPase-2 domain for degradation of Fru-2,6,-P2 is a HP2 domain, evidenced by sequence, mechanistic and structural similarity with histidine phosphatases. | * The phosphatase FBPase-2 domain for degradation of Fru-2,6,-P2 is a HP2 domain, evidenced by sequence, mechanistic and structural similarity with histidine phosphatases. | ||
| − | === | + | === Functions === |
| − | PFKFB is a homodimeric bifunctional enzyme that catalyses both the synthesis and degradation of Fru-2,6-P2 (fructose 2,6-bisphosphate) that is a signal molecule that controls glycolysis <cite>rider04, michel06</cite>. | + | PFKFB is a homodimeric bifunctional enzyme that catalyses both the synthesis and degradation of Fru-2,6-P2 (fructose 2,6-bisphosphate) that is a signal molecule that controls glycolysis <cite>rider04, michel06</cite>. Fru-2,6,-P2 is also the substrate of TIGAR, another subfamily in HP1 family. |
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=== References === | === References === | ||
Revision as of 18:44, 2 June 2015
Phosphatase Classification: Fold HP: Superfamily HP (histidine phosphatase): HP, branch1 family: Subfamily PFKFB
PFKFB stands for PFK-2 (6-phosphofructo-2-kinase)/ FBPase-2 (fructose-2,6-bisphosphatase), which catalyses both the synthesis and degradation of fructose 2,6-bisphosphate (Fru-2,6-P2). Fru-2,6-P2 is a signal molecule that controls glycolysis.
Evolution
PFKFB has two enzymatic domains responsible for the synthesis and hydrolysis, 6-phosphofructo-2-kinase (PFK-2) and fructose-2,6-bisphosphatase (FBPase-2). Both domains are present in all major eukaryotic groups. Previous bioinformatics analysis suggested that PFKFB emerged through gene fusion event that happened in a common ancestor of all extant eukaryotes. 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].
Multiple copies are found in the genomes of different phylogenetic lineages, which emerged through gene duplications, independently in different lineages of many unicellular eukaryotes. In some lineages, one of the domains of the different PFK-2/FBPase-2 isoforms has undergone substitutions of critical catalytic residues or deletions of the whole domain, which rendered some enzymes monofunctional. In a considerable number of other unicellular eukaryotes, mainly parasitic organisms, the enzyme seems to have been lost altogether.
Domain
PFKFB has two domains for its two functions [1, 3]:
- The kinase PFK-2 domain for synthesis of Fru-2,6-P2, has the same fold with adenylate kinase, confirmed by crystal structure.
- The phosphatase FBPase-2 domain for degradation of Fru-2,6,-P2 is a HP2 domain, evidenced by sequence, mechanistic and structural similarity with histidine phosphatases.
Functions
PFKFB is a homodimeric bifunctional enzyme that catalyses both the synthesis and degradation of Fru-2,6-P2 (fructose 2,6-bisphosphate) that is a signal molecule that controls glycolysis [1, 3]. Fru-2,6,-P2 is also the substrate of TIGAR, another subfamily in HP1 family.
References
- Rider MH, Bertrand L, Vertommen D, Michels PA, Rousseau GG, and Hue L. 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis. Biochem J. 2004 Aug 1;381(Pt 3):561-79. DOI:10.1042/BJ20040752 |
- Michels PA and Rigden DJ. Evolutionary analysis of fructose 2,6-bisphosphate metabolism. IUBMB Life. 2006 Mar;58(3):133-41. DOI:10.1080/15216540600688280 |
