ATP-grasp

In molecular biology, the ATP-grasp fold is a unique ATP-binding protein structural motif made of two α+β subdomains that "grasp" a molecule of ATP between them. ATP-grasp proteins have ATP-dependent carboxylate-amine/thiol ligase activity.^[2][3]

ATP-grasp domain
Cartoon representation of the X-ray crystal structure of glycinamide ribonucleotide synthetase from Escherichia coli. , which belongs to the ATP grasp superfamily (PDB: 1gso​).[1]
Identifiers
Symbol	ATP-grasp
Pfam	PF02222
Pfam clan	CL0179
ECOD	206.1.3
InterPro	IPR013815
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Structure

Proteins of the ATP-grasp family have an overall structural configuration organised into three domains referred to as the N-terminal domain (or A-domain), the central domain (or B-domain), and the C-terminal domain (or C-domain).^[3]

Function

ATP-grasp enzymes catalyse the ATP-dependent ligation of a carboxylate-containing molecule to an amino or thiol group-containing molecule. The reactions typically involve formation of acylphosphate intermediates. These enzymes are involved in various metabolic pathways including purine biosynthesis, fatty acid synthesis, and gluconeogenesis.^[4]

Examples of proteins containing this domain

• D-alanine-D-alanine ligase
• glutathione synthetase
• biotin carboxylase
• carbamoyl phosphate synthetase
• ribosomal protein S6 modification enzyme (RimK)
• urea amidolyase
• tubulin-tyrosine ligase
• enzymes involved in purine biosynthesis.

Evolution and distribution

The ATP-grasp fold is evolutionarily conserved across different enzyme families and its presence is ubiquitous across prokaryotes and eukaryotes.^[3]

Use in research

Researchers have developed several types of inhibitors for these enzymes, including mechanism-based inhibitors, ATP-competitive inhibitors, and non-competitive inhibitors. Some ATP-grasp enzymes are being studied as potential targets for antibiotics and anti-obesity drugs.^[3]