InterPro domain: IPR013815

The ATP-grasp fold is one of several distinct ATP-binding folds, and is found in enzymes that catalyse the formation of amide bonds, catalysing the ATP-dependent ligation of a carboxylate-containing molecule to an amino or thiol group-containing molecule [ 1 ]. This fold is found in many different enzyme families, including various peptide synthetases, biotin carboxylase, synapsin, succinyl-CoA synthetase, pyruvate phosphate dikinase, and glutathione synthetase, amongst others [ 2 ]. These enzymes contribute predominantly to macromolecular synthesis, using ATP-hydrolysis to activate their substrates.

The ATP-grasp fold shares functional and structural similarities with the PIPK (phosphatidylinositol phosphate kinase) and protein kinase superfamilies. The ATP-grasp domain consists of two subdomains with different alpha+beta folds, which grasp the ATP molecule between them. Each subdomain provides a variable loop that forms part of the active site, with regions from other domains also contributing to the active site, even though these other domains are not conserved between the various ATP-grasp enzymes [ 3 ].

This entry represents subdomain 1 found at the N-terminal end of the ATP-grasp domain.

1. A diverse superfamily of enzymes with ATP-dependent carboxylate-amine/thiol ligase activity. Protein Sci. 6, 2639-43
2. Mutational analysis of ATP-grasp residues in the two ATP sites of Saccharomyces cerevisiae carbamoyl phosphate synthetase. Arch. Biochem. Biophys. 407, 1-9
3. A common fold for peptide synthetases cleaving ATP to ADP: glutathione synthetase and D-alanine:d-alanine ligase of Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 92, 1172-6