cd00228: ATP-grasp_Superfamily (This model is not part of the current CDD release)
ATP-grasp superfamily
The defining feature of ATP-grasp superfamily members is that they all display carboxylate-amine/thiol ligase activity while acting on a diverse range of substrates. The C-terminal domain and the central domain predominantly form the nucleotide and substrate-binding sites which makes the catalytic core. These enzymes catalyze an ATP-dependent ligation of a carboxyl group carbon of one substrate with an amino or imino group nitrogen of the second one via the formation of an acylphosphate intermediate. They also share a conserved Mg-ATP-binding domain that is believed to undergo a conformational change on substrate binding. Each member of the ATP-Grasp superfamily is known to bind one or more divalent metal ions at the catalytic site, and all but synapsin (which binds a single Ca ion) utilizes Mg ion as the physiological cofactor. A few members of this family (eukaryotic glutathione synthetase, glutathionylspermidine synthase, and trypanothione synthetase) display a rare gene permutation which results into a circular shift of the conserved secondary structure. In spite of the circular permutation, the resulting protein forms a very similar active site. As a result, 'circularly-permuted' members display the same catalytic mechanism as the 'non-circularly permuted' members of this superfamily. It has been suggested that this rare gene permutation must have occurred before the evolution of eukaryotes.
Structure:2HGS: Human circularly permuted glutathione synthetase (hGS) in complex with glutathione, ADP, SO4, and two Mg ions; contacts determined at 4 A
Jiyao W et al.(2023). "The conserved domain database in 2023.",