Fructose Bisphosphate Aldolase: Difference between revisions
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As an enzyme, the aldolase must not only encourage and favor the hydrolysis of fructose 1,6-bisphosphate, but also bind the substrate so as to hold it in the active site. The main-chain nitrogens of Ser271 and Gly272 hold the 1-phosphate group while the Lys41, Arg42 and Arg303 residues hold the 6-phosphate group. The five proposed binding residues are in close proximity to the catalytic Lys229, implicating them as participants in the binding process.<ref>Dalby, Andrew, Zbigniev Dauter, and Jennifer Littlechild. "Crystal structure of human muscle aldolase complexed with fructose 1,6 bisphosphate: Mechanistic implications." Protein Science. 8 (1999): 291-297. Print.</ref> | As an enzyme, the aldolase must not only encourage and favor the hydrolysis of fructose 1,6-bisphosphate, but also bind the substrate so as to hold it in the active site. The main-chain nitrogens of Ser271 and Gly272 hold the 1-phosphate group while the Lys41, Arg42 and Arg303 residues hold the 6-phosphate group. The five proposed binding residues are in close proximity to the catalytic Lys229, implicating them as participants in the binding process.<ref>Dalby, Andrew, Zbigniev Dauter, and Jennifer Littlechild. "Crystal structure of human muscle aldolase complexed with fructose 1,6 bisphosphate: Mechanistic implications." Protein Science. 8 (1999): 291-297. Print.</ref> | ||
The reaction is an aldol cleavage, or otherwise termed, retro aldo condensation. Catalysis occurs first when the nucleophilic ε-amine group of Lys229 attacks the carbonyl (alpha) carbon of the substrate (FBP) in its open-ring state, pushing an electron pair to the oxygen of the carbonyl. The oxygen is protonated and leaves as water as a protonated <scene name='Austin_Drake_Sandbox/Schiff_base/2'>Schiff base</scene> is produced (an imine resulting from a ketone and amine) with the open-ring form of FBP, accompanied by electrostatic stabilization from <scene name='Austin_Drake_Sandbox/Catalytic_site_w_water/4'>Asp33</scene>. Aldol cleavage between C3 and C4 produces GAP and an enamine precursor to DHAP. Tautomerization, protonation and the hydrolysis of the Schiff base produce the final product of DHAP and regenerate the enzyme. The catalysis is driven by the more favorable stability of the protonated Schiff base compared to the enolate that would appear in basic catalysis pathways | The reaction is an aldol cleavage, or otherwise termed, retro aldo condensation. Catalysis occurs first when the nucleophilic ε-amine group of Lys229 attacks the carbonyl (alpha) carbon of the substrate (FBP) in its open-ring state, pushing an electron pair to the oxygen of the carbonyl. The oxygen is protonated and leaves as water as a protonated <scene name='Austin_Drake_Sandbox/Schiff_base/2'>Schiff base</scene> is produced (an imine resulting from a ketone and amine) with the open-ring form of FBP, accompanied by electrostatic stabilization from <scene name='Austin_Drake_Sandbox/Catalytic_site_w_water/4'>Asp33</scene>. Aldol cleavage between C3 and C4 produces GAP and an enamine precursor to DHAP. Tautomerization, protonation and the hydrolysis of the Schiff base produce the final product of DHAP and regenerate the enzyme. The catalysis is driven by the more favorable stability of the protonated Schiff base compared to the enolate that would appear in basic catalysis pathways.<ref name="book" /> | ||
The enzyme is an a/B protein. It is part of the aldolase superfamily and the class I aldolases.<ref>Protein: fructose-1,6-bisphosphate aldolase from human (homo sapiens), muscle isozyme. (2009). Retrieved from http://scop.mrc-lmb.cam.ac.uk</ref><scene name='Austin_Drake_Sandbox/Different_colors/1'> a Helices and B sheets</scene> can be seen in their specific regions concentrically located around the active site. <scene name='Austin_Drake_Sandbox/B_sheet_barrel/2'>FBP is catalyzed inside the barrel.</scene> | The enzyme is an a/B protein. It is part of the aldolase superfamily and the class I aldolases.<ref>Protein: fructose-1,6-bisphosphate aldolase from human (homo sapiens), muscle isozyme. (2009). Retrieved from http://scop.mrc-lmb.cam.ac.uk</ref><scene name='Austin_Drake_Sandbox/Different_colors/1'> a Helices and B sheets</scene> can be seen in their specific regions concentrically located around the active site. <scene name='Austin_Drake_Sandbox/B_sheet_barrel/2'>FBP is catalyzed inside the barrel.</scene> | ||