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PhosphofructokinasePhosphofructokinase
Phosphofructokinase (PFK) (PDB id 4pfk) is an approximately 300 residue enzyme that catalyzes the phosphorylation of Fructose-6-phosphate (F6P) to Fructose-1,6-bisphosphate (F1,6P). It is a Homotetramer that acts as a dimer of dimers, similar to hemoglobin.[1] One half of each dimer is involved in the binding of ATP, while the other is involved with substrate binding and also contains an allosteric site. [2] The Secondary Structure puts it in an alpha and beta class. Each unit is comprised of two domains that sandwich parallel beta sheets inbetween alpha helices. The outer most beta sheets of the larger domain, however, are anti-parallel. This is best seen in the 4pfk image Phosphofructokinase is not only the enzymes name, but also, the fold, superfamily, and family classification name. While PFK in glycolysis is an ATP-dependent phosphofructokinase, Pyrophosphate-dependent phosphofructokinases exist as well. Contents [hide]
1 Role in Glycolysis 2 Mechanism and Regulation of Phosphofructokinase 3 Additional Resources 4 References
[edit] Role in Glycolysis
Glycolysis is the process for preparing, and breaking down, glucose to make pyruvic acid, which is used in anaerobic respiration or as one of the starting reactants in the citric acid cycle. Three points in the process of glycolysis occur with a large negative free energy and are therefore, irreversible. These three points are hexokinase, phosphofructokinase, and pyruvate kinase; of these three PFK is considered the major regulatory point for glycolysis in muscle with a ΔG= -25.9 kJ/mol. [3] [edit] Mechanism and Regulation of Phosphofructokinase
Phosphofructokinase binds both Mg2+-ATP and fructose-6-phosphate (F6P) to make fructose-1,6-bisphosphate and Mg2+-ADP. Although the image with both of these products has not been determined, F6P and Mg2+-ADP bound to the enzyme has been. There are three ligand binding sites per subunit. Two make up the active site, which binds F6P and ATP, while the third is an allosteric binding site.[4] Some proposed residues involved at the active site include ASP 127 and ARG 171.[5] PFK exist in two conformational states, both R and T states which are in equilibrium. ATP binds both active and allosteric sites in both conformations. While ATP binds the active site equally well, it preferentially binds the allosteric site of the T state [6] This preferential binding causes a shift from equilibrium of the two states, to a greater amount of T state [7], which decreases the affinity for F6P. Allosteric activator ADP also binds to allosteric site to increase the ratio of R state phosphofructokinase. Along with ADP,AMP and F2,6P inhibit the regulatory role of ATP. The PFK's Km for ATP is .020mM and .032mM.[8]
Image:PFK mech.JPG [edit] Additional Resources
For additional information, see: Carbohydrate Metabolism [edit] References
↑ Evans PR, Farrants GW, Hudson PJ. Phosphofructokinase: structure and control. Philos Trans R Soc Lond B Biol Sci. 1981 Jun 26;293(1063):53-62. PMID:6115424 ↑ Shirakihara Y, Evans PR. Crystal structure of the complex of phosphofructokinase from Escherichia coli with its reaction products. J Mol Biol. 1988 Dec 20;204(4):973-94. PMID:2975709 ↑ Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, 2008. Print. ↑ Evans PR, Farrants GW, Hudson PJ. Phosphofructokinase: structure and control. Philos Trans R Soc Lond B Biol Sci. 1981 Jun 26;293(1063):53-62. PMID:6115424 ↑ http://www.nature.com/nature/journal/v327/n6121/abs/327437a0.html ↑ Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, 2008. Print. ↑ PubMed:2136935 ↑ Campos G, Guixe V, Babul J. Kinetic mechanism of phosphofructokinase-2 from Escherichia coli. A mutant enzyme with a different mechanism. J Biol Chem. 1984 May 25;259(10):6147-52. PMID:6233271
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