Fructose-1,6-Bisphosphate Aldolase

Class I aldolases are highly conserved homotetrameric enzymes.  Fructose-1,6-bisphosphate aldolase is found in the glycolytic and gluconeogenic pathways. This enzyme is responsible for the reversible reaction catalyzing the aldol cleavage from fructose-1,6-bisphophate (FBP) into dihydoxyacetone phosphate (DHAP) and glyceraldehydes-3-phosphate (GAP).  This lyase is in the Alpha Beta class and has a barrel architecture.  It has a TIM barrel topology and belongs to the Aldolase class I homologous superfamily.(1) In the malaria parasite Plasmodium falciparum the glycoltic pathway utilizing the aldolase occurs outside the mitochondria.  As previously stated the reaction catalyzed by the aldolase is reversible but it is favorably in the forward direction (glycolosis). 

 Each monomer of this homotetrameric protein is composed of an (a/b)barrel(3).  The strands of the barrel are arranged into a parallel b-sheet.  This sheet wraps around to form the barrel. By clicking on the "View ß-barrels" button, two of the barrels can be seen. Remember this is only half of the enzyme (full enzyme would contain four barrels).

The center of this barrel is the active site of the enzyme. This can be obseved using the "Active Site" button. 

The active site is composed largely of charged and polar amino acid residues, these include Asp-39, Lys-115, Lys-144, Glu-194, Lys-236, and Ser-278. Along with facilitating catalysis, these polar residues contribute to the enzymes ability to bind substrate and help stabilize the intermediates.

The catalytic mechanism of this enzyme proceeds through a Schiff base intermediate, which is a covalent adduct formed by the nucleophilic attack of the nitrogen from a critical lysine on the C2 carbonyl of FBP(4).  Lys-236 residue is responsible for the nucleophilic attack of this nitrogen, which forms the Schiff base. Glu-194 is in the perfect postion to act as the proton donor facilitating the cleavage of the carbon-cabon bond, Resulting in the two three carbon products.

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