Fructose Bisphosphate Aldolase: Difference between revisions
Austin Drake (talk | contribs) No edit summary |
Austin Drake (talk | contribs) No edit summary |
||
| Line 3: | Line 3: | ||
'''Introduction and Structure''' | '''Introduction and Structure''' | ||
<scene name='Austin_Drake_Sandbox/Tetramer/3'>Fructose bisphosphate aldolase</scene> is an enzyme in glycolysis. It catalyzes the cleavage of fructose-1,6-bisphosphate into dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP). It can also catalyze the cleavage of fructose 1-phosphate to diydroxyacetone and glyceraldehyde. Different isozymes exhibit preferences for either or both of the substrates. | <scene name='Austin_Drake_Sandbox/Tetramer/3'>Fructose bisphosphate aldolase</scene> is an enzyme in glycolysis. It catalyzes the cleavage of fructose-1,6-bisphosphate into dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP). It can also catalyze the cleavage of fructose 1-phosphate to diydroxyacetone and glyceraldehyde (GA). Different isozymes exhibit preferences for either or both of the substrates, depending on the role of the aldolase (i.e. gluconeogenesis versus glycolysis). | ||
The reaction is an aldol cleavage, or otherwise termed, retro aldo condensation. Catalysis occurs | While it can exist as a monomer, it normally exists as a homotetramer. Each monomeric unit consists of nine alpha helices and eight beta sheets. | ||
'''Binding and Catalysis''' | |||
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 Schiff base 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/3'>Asp33</scene>. Aldol cleavage between C3 and C4 produces GAP and an enamine precursor to DHAP. Tautomerization, protonation and the hydrolysis of the Schiff's base produce the final product of DHAP and regenerates the enzyme.<ref>Voet, D, Voet, J, & Pratt, C. (2008). Fundamentals of biochemistry, third edition. Hoboken, NJ: Wiley & Sons, Inc.</ref> The enzyme is an a/B protein. It is part of the aldolase superfamily and the class I aldoses<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> | |||
{{STRUCTURE_2ald | PDB=2ald | SCENE= }} | {{STRUCTURE_2ald | PDB=2ald | SCENE= }} | ||
'''References''' | '''References''' | ||
<references/> | <references/> | ||
Revision as of 07:08, 18 March 2010
Fructose bisphosphate aldolaseFructose bisphosphate aldolase
Introduction and Structure
is an enzyme in glycolysis. It catalyzes the cleavage of fructose-1,6-bisphosphate into dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP). It can also catalyze the cleavage of fructose 1-phosphate to diydroxyacetone and glyceraldehyde (GA). Different isozymes exhibit preferences for either or both of the substrates, depending on the role of the aldolase (i.e. gluconeogenesis versus glycolysis).
While it can exist as a monomer, it normally exists as a homotetramer. Each monomeric unit consists of nine alpha helices and eight beta sheets.
Binding and Catalysis 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.[1]
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 Schiff base is produced (an imine resulting from a ketone and amine) with the open-ring form of FBP, accompanied by electrostatic stabilization from . Aldol cleavage between C3 and C4 produces GAP and an enamine precursor to DHAP. Tautomerization, protonation and the hydrolysis of the Schiff's base produce the final product of DHAP and regenerates the enzyme.[2] The enzyme is an a/B protein. It is part of the aldolase superfamily and the class I aldoses[3] can be seen in their specific regions concentrically located around the active site. Template:STRUCTURE 2ald
References
- ↑ 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.
- ↑ Voet, D, Voet, J, & Pratt, C. (2008). Fundamentals of biochemistry, third edition. Hoboken, NJ: Wiley & Sons, Inc.
- ↑ Protein: fructose-1,6-bisphosphate aldolase from human (homo sapiens), muscle isozyme. (2009). Retrieved from http://scop.mrc-lmb.cam.ac.uk