Glutathione synthetase

Function

Glutathione synthetase (GSS) is an ATP-dependent enzyme which catalyzes the condensation of γ-glutamylcysteine and glycine to glutathione. GSS is part of the glutathione biosynthesis pathway. Glutathione Synthetases are a class of enzymes that work catalyze the chemical reaction

ATP + γ-L-glutamyl-L-cysteine + glycine ↔ ADP + phosphate + glutathione

Human Glutathione Synthase participates in glutamate metabolism and glutathione metabolism; its three substrates are ATP, gamma-L-glutamyl-L-cysteine, and glycine. Its three products are ADP, phosphate, and glutathione. At least one compound, Phosphinate, is known to inhibit this enzyme.

The enzyme is also a member of the ATP-Grasp family of proteins, so its method of binding is similar to others in the ATP-Grasp family. However, it lacks significant sequence identity with other members of the family, even though its structure is circular permutation of other known structures in the family.

Role in Human Disease^[1]

This enzyme's action produces glutathione, a vital and abundant tripeptide that is found in most living cells. In humans, mutations to hGS can lead to lowered levels of glutathione, causing a range of disease states. Lowered levels of glutathione have been associated with diseases such as human immunodeficiency, hepatitis C, type II diabetes, ulcerative colitis, idiopathic pulmonary fibrosis, adult respiratory distress syndrome, and cataracts.

Common Mutations^[2]

Structural highlights

GSS active site is situated at one edge of a parallel β sheet^[3].