PGLS Human

6PGL is a cytosolic enzyme found in all organisms. In humans, it exists as a monomer composed of 258 amino acid residues with a molecular mass of approximately 30 kDa . The enzyme’s tertiary structure employs an α/β hydrolase fold, with active site residues clustered on the loops of the α-helices . The stability of the enzyme’s structure is reinforced through salt bridges between aspartic acid and arginine residues, as well as aromatic side-chain stacking interactions .

The hydrolysis reaction catalyzed by 6PGL proceeds via proton transfer to the O5 ring oxygen atom, similar to the mechanisms of xylose isomerase and ribose-5-phosphate isomerase . The reaction initiates with the attack of a hydroxide ion at the C5 ester, forming a tetrahedral intermediate. The elimination of the ester linkage follows, aided by the donation of a proton from an active site histidine residue . Molecular dynamic simulations have shown that the histidine residue is responsible for proton transfer, while arginine residues stabilize the negatively charged phosphate group .

6PGL plays a vital role in the PPP, which is responsible for producing ribulose 5-phosphate and NADPH. These products are essential for nucleotide synthesis and providing reducing equivalents for various biosynthetic reactions . The enzyme’s activity is crucial for maintaining cellular redox balance and supporting anabolic processes.

Recombinant 6PGL is produced using genetic engineering techniques, where the human gene encoding 6PGL is inserted into an expression vector and introduced into a host organism, such as bacteria or yeast. The host organism then expresses the human enzyme, which can be purified for research or therapeutic purposes.

Recombinant 6PGL is used in various research applications to study the enzyme’s structure, function, and role in metabolic pathways. It is also utilized in drug discovery efforts, particularly in targeting metabolic pathways associated with diseases such as cancer and parasitic infections .