Sandbox/Judy Voet/PFK: Difference between revisions
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<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' /> | ||
PFK from B. stearothermophilus 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. | PFK from B. stearothermophilus 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. | ||
Two of the active sites of the enzyme are located at the interface of subunits A (light Blue) and D (yellow) and two at the interface of subunits B (green) and C (pink). Two of the allosteric sites are located at the interface of subunits A and B and two at the interface of subunits C and D. Here is a closeup of the <scene name='Sandbox/Judy_Voet/PFK/Pfk_ad_closeup/1'>A/D interface active site</scene> of subunit D (Yellow). Note that amino acids from subunit A (light blue) also contribute to the binding of F6P. Also here is a closeup of the <scene name='Sandbox/Judy_Voet/PFK/Pfk_ab_closeup/1'>A/B allosteric site</scene>of subunit B with contributions from both subunits to the binding of ADP. | Two of the active sites of the enzyme are located at the interface of subunits A (light Blue) and D (yellow) and two at the interface of subunits B (green) and C (pink). Two of the allosteric sites are located at the interface of subunits A and B and two at the interface of subunits C and D. Here is a closeup of the <scene name='Sandbox/Judy_Voet/PFK/Pfk_ad_closeup/1'>A/D interface active site</scene> of subunit D (Yellow). Note that amino acids from subunit A (light blue) also contribute to the binding of F6P. Also here is a closeup of the <scene name='Sandbox/Judy_Voet/PFK/Pfk_ab_closeup/1'>A/B allosteric site</scene> of subunit B with contributions from both subunits to the binding of ADP. | ||
This Kinemage exercise consists of two kinemage scenes that illustrate some of the allosterically-induced conformational changes that occur in PFK from Bacillus stearothermophilus. | This Kinemage exercise consists of two kinemage scenes that illustrate some of the allosterically-induced conformational changes that occur in PFK from Bacillus stearothermophilus. | ||