Sandbox Reserved 796

From Proteopedia

Introduction and General Structure

is an enzyme in glycolysis, the metabolic pathway that converts glucose into pyruvate and produces cellular energy in form of ATP (adenosine triphosphate). Aldolase catalyzes an aldol cleavage reaction that hydrolyzes fructose 1,6-bisphosphate into glycerone phosphate and glyceraldehyde 3-phosphate. Fructose-1,6-bisphosphate aldolase is a tetramer, has alpha helices in pinkish purple and beta sheets in blue. The alpha helices are mostly found on the surface (outside) of the enzyme while the beta sheets are embedded in the inside of the enzyme; which might indicate that most of polar amino acids are located on the peripheral helices, while hydrophobic or paired-polar amino acids are found within the beta sheets.

Hydrogen and Disulfide Bond

are in black and there is no observable disulfide bond in the enzyme. Hydrogen bonding holds the molecule together (especially in secondary structure) and stabilizes the enzyme. Based on the position of the hydrogen bonds, we concluded that the beta sheets are parallel to each other since the H-bonds are slanted between sheets.

Hydrophobic and Hydrophilic Residues

The are in orange while the are in teal. The hydrophobic residues are mostly observed in the interior of the enzyme,away from the aqueous solvent(possibly on the beta sheets). The hydrophilic residues are mostly located on the alpha helices (on the outside of this enzyme)which interact with the aqueous solvent. Based on this model, we can conclude that the enzyme is made out of a roughly equal amount of both hydrophobic and hydrophilic residues.

Solvent

(colored in cream) surrounded the surface of the enzyme, which indicated that the residues that made up the surface of the enzyme is hydrophilic (as observed above). With 50% transparency, no water molecules is observed to be inside the enzyme, which indicated that the inner surface of the enzyme must be hydrophobic.

The ligands and ligand contacts

(for chain A) is in purple (the substrate is a glyceraldehyde 3-phosphate analog). There are three other 1,3-Dihydroxyacetonephosphate molecules the other subunits (B, C, and D). Zinc (which is not shown in the enzyme structure) is an cofactor that involves in the aldol reaction of aldolase but is not significant in stabilizing the enzyme. are Ser271, Gly272, Gly302, Lys229, Arg303, Lys146 and Asn33 (colored in reddish brown) interact and stabilize the substrate (colored in pinkish red).

Catalytic Residues

are Asn33(A)-Glu187(A)-Lys229(A)(in red)while the substrate is in mint. The lysine residue has the major role in the molecule's catalysis. Asn33-Glu187-Lys229 help catalyze an aldol cleavage reaction that hydrolyzes fructose 1,6-bisphosphate into glycerone phosphate and glyceraldehyde 3-phosphate.The positive charge present on the side chain's nitrogen atom attacks a carbon found within the substrate to begin catalysis. Same residues are observed in other subunits (B, C and D).

References

1. M.St-Jean et al. (2009). Charge stabilization and entropy reduction of central lysine residues in fructose-bisphosphate aldolase. Biochemistry, 48, 4528-4537. PubMed id: 19354220 DOI: 10.1021/bi8021558

2. http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

3. http://www.rcsb.org/pdb/explore/explore.do?structureId=3DFO