Human and yeast glutathione synthetases are homodimers, meaning they are composed of two identical subunits of itself non-covalently bound to each other.
On the other hand, E. coli glutathione synthetase is a homotetramer.
Nevertheless, they are part of the ATP-grasp superfamily, which consists of 21 enzymes that contain an ATP-grasp fold.
Each subunit interacts with each other through alpha helix and beta sheet hydrogen bonding interactions and contains two domains.
One domain facilitates the ATP-grasp mechanism and the other is the catalytic active site for γ-glutamylcysteine.
The ATP-grasp fold is conserved within the ATP-grasp superfamily and is characterized by two alpha helices and beta sheets that hold onto the ATP molecule between them.
The domain containing the active site exhibits interesting properties of specificity.
In contrast to γ-glutamylcysteine synthetase, glutathione synthetase accepts a large variety of glutamyl-modified analogs of γ-glutamylcysteine, but is much more specific for cysteine-modified analogs of γ-glutamylcysteine.
Crystalline structures have shown glutathione synthetase bound to GSH, ADP, two magnesium ions, and a sulfate ion.
Two magnesium ions function to stabilize the acylphosphate intermediate, facilitate binding of ATP, and activate removal of phosphate group from ATP.
Sulfate ion serves as a replacement for inorganic phosphate once the acylphosphate intermediate is formed inside the active site.

As of late 2007, 7 structures have been solved for this class of enzymes, with PDB accession codes 1GLV, 1GSA, 1GSH, 1M0T, 1M0W, 2GLT, and 2HGS.
Human and yeast glutathione synthetases are homodimers, meaning they are composed of two identical subunits of itself non-covalently bound to each other. On the other hand, E. coli glutathione synthetase is a homotetramer. Nevertheless, they are part of the ATP-grasp superfamily, which consists of 21 enzymes that contain an ATP-grasp fold. Each subunit interacts with each other through alpha helix and beta sheet hydrogen bonding interactions and contains two domains. One domain facilitates the ATP-grasp mechanism and the other is the catalytic active site for γ-glutamylcysteine. The ATP-grasp fold is conserved within the ATP-grasp superfamily and is characterized by two alpha helices and beta sheets that hold onto the ATP molecule between them. The domain containing the active site exhibits interesting properties of specificity. In contrast to γ-glutamylcysteine synthetase, glutathione synthetase accepts a large variety of glutamyl-modified analogs of γ-glutamylcysteine, but is much more specific for cysteine-modified analogs of γ-glutamylcysteine. Crystalline structures have shown glutathione synthetase bound to GSH, ADP, two magnesium ions, and a sulfate ion. Two magnesium ions function to stabilize the acylphosphate intermediate, facilitate binding of ATP, and activate removal of phosphate group from ATP. Sulfate ion serves as a replacement for inorganic phosphate once the acylphosphate intermediate is formed inside the active site.
As of late 2007, 7 structures have been solved for this class of enzymes, with PDB accession codes 1GLV, 1GSA, 1GSH, 1M0T, 1M0W, 2GLT, and 2HGS.
Glutathione synthetase