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ATP-grasp-like domain Glutathione biosynthesis is achieved in most organisms via a conserved two-step approach relying on the capacity of two independent and unrelated ligases to perform peptide synthesis coupled to ATP hydrolyzis. In a first and rate-limiting step, gamma-glutamylcysteine ligase (gamma-ECL) (or GshA; EC:6.3.2.2) uses l-glutamate and l-cysteine to form gamma-glutamylcysteine (gamma-EC), which, in a second step, is condensed with glycine to glutathione by glutathione synthetase (GS) (or GshB; EC:6.3.2.3). However, several pathogenic and free-living bacteria carry out glutathione biosynthesis based on a single enzyme that catalyzes both the gamma-ECL and the GS reactions. Such bifunctional glutathione-synthesizing enzymes have been termed gamma-GCS-GS or GshF. Hybrid GshF contains a typical gamma-proteobacterial gamma-ECL fused to an ATP-grasp-like domain. The ATP-grasp-like module is responsible for the ensuing formation of glutathione from gamma-glutamylcysteine and glycine. The ATP-grasp-like domain has an antiparallel beta-sheet in the GshF structures in contrast to all structurally characterized members of the ATP-grasp superfamily. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",