2-dehydro-3-deoxy-phosphogluconate Aldolase - Enzyme Structure

Enzyme Structure

KDPG Aldolase was recently determined to be a trimer through crystallographic three-fold symmetry, with 225 residues. The enzyme was determined to have a molecular weight of 23,942. The trimer is stabilized primarily through hydrophobic interactions. The molecule has tertiary folding similar to triosephosphate isomerase and the A-domain of pyruvate kinase, forming an eight strand α/β-barrel structure. The α/β-barrel structure is capped on one side by the N-terminal helix. The other side, the carboxylic side, contains the active site. Each subunit contains a phosphate-ion bound in position of the aldolase biding site. It has been found that there are four cysteinyl groups present in each subunit, with two readily accessible and two buried in the subunit.

The active site contains the zwitterionic pair Glu-45/Lys-133. The Lysine, which is involved in the formation of the Schiff base is coordinated by a phosphate ion and two solvent water molecules. The first water molecule serves as a shuttle between the Glutamate and the substrate, staying bound to the enzyme throughout the catalytic cycle. The second water molecule is a product of the dehydration of the carbinolamine that leads to the formation of the Schiff base. It also functions as the nucleophile during hydrolysis of the enzyme-product Schiff base, leading to the release of pyruvate.

As of late 2007, 13 structures have been solved for this class of enzymes, with PDB accession codes 1EUA, 1EUN, 1FQ0, 1FWR, 1KGA, 1MXS, 1WA3, 1WAU, 1WBH, 2C0A, 2NUW, 2NUX, and 2NUY.