The ATP-grasp superfamily currently includes 17 groups of enzymes, catalyzing ATP-dependent ligation of a carboxylate containing molecule to an amino or thiol group-containing molecule [1]. They contribute predominantly to macromolecular synthesis. ATP-hydrolysis is used to activate a substrate. For example, DD-ligase transfers phosphate from ATP to D-alanine on the first step of catalysis. On the second step the resulting acylphosphate is attacked by a second D-alanine to produce a DD dipeptide following phosphate elimination [2].

The ATP-grasp domain contains three conserved motifs, corresponding to the phosphate binding loop and the Mg(2+) binding site [3]. The fold is characterized by two α-β subdomains that grasp the ATP molecule between them (see <PDB:1IOW>). Each subdomain provides a variable loop that forms a part of the active site, completed by region of other domains not conserved between the various ATP-grasp enzymes[4].

Proteins known to contain an ATP-grasp domain are listed below:

• Biotin carboxylase (EC 6.3.4.14).
• Carbamoyl-phosphate synthase (EC 6.3.5.5).
• Cyanophycin synthetase (EC 6.-.-.-).
• D-alanine--D-alanine ligase (EC 6.3.2.4).
• Urea amidolyase (Urea carboxylase) (EC 6.3.4.6).
• Glutathione synthetase (EC 6.3.2.3).
• Lysine biosynthesis protein.
• Methylcrotonyl-CoA carboxylase (EC 6.4.1.4).
• MurC/ddl bifunctional enzyme (EC 6.3.2.8).
• Propionyl-CoA carboxylase (EC 6.4.1.3).
• Phosphoribosylamine--glycine ligase (EC 6.3.4.13).
• Phosphoribosylaminoimidazole carboxylase (EC 4.1.1.21).
• Pyruvate carboxylase 1 (EC 6.4.1.1).
• CAD protein, includes carbamoyl-phosphate synthase activity.
• Ribosomal protein S6 modification protein.
• Succinyl-CoA synthetase (EC 6.2.1.5).
• Vancomycin/teicoplanin resistance protein (EC 6.3.2.-).
• 5-(carboxyamino)imidazole ribonucleotide synthase (EC 6.3.4.18).
• Inositol-tetrakisphosphate 1-kinase (EC 2.7.1.134).
• Inositol-1,3,4-trisphosphate 5/6-kinase (EC 2.7.1.159).

The profile we developed covers the entire ATP-grasp domain.