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.

Structure

Proteins of the ATP-grasp family have an overall structural configuration organised into three domains referred to as the N-terminal domain, the central domain, and the C-terminal domain.

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.

Examples of proteins containing this domain

D-alanine-D-alanine ligase
glutathione synthetase
biotin carboxylase
carbamoyl phosphate synthetase
ribosomal protein S6 modification enzyme
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.

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.