Phosphofructokinase (PFK): Difference between revisions

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New page: ==Overview== Phosphofructokinase (PFK) is a glycolytic enzyme that catalyzes the transfer of a phosphoryl group from ATP to fructose-6-phosphate (F6P) to yield ADP and fructose-1,6-bispho...
 
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==Overview==
==Overview==
Phosphofructokinase (PFK) is a glycolytic enzyme that catalyzes the transfer of a phosphoryl group from ATP to fructose-6-phosphate (F6P) to yield ADP and fructose-1,6-bisphosphate (FBP). The PFK reaction is strongly exergonic (irreversible) under physiological conditions and hence is one of the glycolytic pathway's rate-determining steps. In most organisms/tissues, PFK is the glycolytic pathway's major flux-regulating enzyme; its activity is controlled by the concentrations of an unusually large number of metabolites including ATP, ADP, AMP, PEP and fructose-2,6-bisphosphate (F2,6P).  
Phosphofructokinase-1 (PFK-1) is a glycolytic enzyme that catalyzes the transfer of a phosphoryl group from ATP to fructose-6-phosphate (F6P) to yield ADP and fructose-1,6-bisphosphate (FBP). The PFK reaction is strongly exergonic (irreversible) under physiological conditions and hence is one of the glycolytic pathway's rate-determining steps. In most organisms/tissues, PFK is the glycolytic pathway's major flux-regulating enzyme; its activity is controlled by the concentrations of an unusually large number of metabolites including ATP, ADP, AMP, PEP and fructose-2,6-bisphosphate (F2,6P).  
<applet load='4pfk' scene='Sandbox/Judy_Voet/PFK/4pfk_biol/1' size='300' frame='true' align='right' caption='PFK: R-state Biological tetramer; generated from 4pfk by QPS' />
<applet load='4pfk' scene='Sandbox/Judy_Voet/PFK/4pfk_biol/1' size='300' frame='true' align='right' caption='PFK: R-state Biological tetramer; generated from 4pfk by QPS' />
<scene name='Sandbox/Judy_Voet/PFK/4pfk_biol/1'>PFK from B. stearothermophilus</scene> is a tetramer of identical 320-residue subunits. It is an allosteric enzyme that is described using the symmetry model of allosterism whereby there is a concerted transition from its high-activity R state to its low-activity T state.  The X-ray structures of both R and T states of the enzyme have been reported.<ref>PMID:2136935</ref> The binding of one molecule of its substrate F6P, which binds to the R state enzyme with high affinity but to the T state enzyme with low affinity, causes PFK to take up the R state, which in turn, increases the binding affinity of the enzyme for additional F6P (a homotropic effect). Activators, such as ADP and AMP bind to so-called allosteric sites, binding sites distinct from the active site, where they likewise facilitate the formation of the R state and hence activate the enzyme (a heterotropic effect; ADP, being a product of the PFK reaction, also binds at the enzyme's active site). Similarly, inhibitors such as PEP bind to allosteric sites (which in the case of PFK overlaps the activating allosteric site) where they promote the formation of the T state, thereby inhibiting the enzyme.  
<scene name='Sandbox/Judy_Voet/PFK/4pfk_biol/1'>PFK from B. stearothermophilus</scene> is a tetramer of identical 320-residue subunits. It is an allosteric enzyme that is described using the symmetry model of allosterism whereby there is a concerted transition from its high-activity R state to its low-activity T state.  The X-ray structures of both R and T states of the enzyme have been reported.<ref>PMID:2136935</ref> The binding of one molecule of its substrate F6P, which binds to the R state enzyme with high affinity but to the T state enzyme with low affinity, causes PFK to take up the R state, which in turn, increases the binding affinity of the enzyme for additional F6P (a homotropic effect). Activators, such as ADP and AMP bind to so-called allosteric sites, binding sites distinct from the active site, where they likewise facilitate the formation of the R state and hence activate the enzyme (a heterotropic effect; ADP, being a product of the PFK reaction, also binds at the enzyme's active site). Similarly, inhibitors such as PEP bind to allosteric sites (which in the case of PFK overlaps the activating allosteric site) where they promote the formation of the T state, thereby inhibiting the enzyme.  
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==References==
==References==
<references/>
<references/>
==External Links==
Wikipedia [http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb50_4.html]
PDB Molecule of the Month [http://en.wikipedia.org/wiki/Phosphofructokinase_1]

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Judy Voet, Eran Hodis, Zach Westrick, David Canner, Michal Harel, Alexander Berchansky, Jaime Prilusky, Joel L. Sussman, Ann Taylor