ATP-grasp
| 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 | ||||||||
| |||||||||
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]
Structure
[edit]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).[4]
Function
[edit]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.[5]
Examples of proteins containing this domain
[edit]- 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
[edit]The ATP-grasp fold is evolutionarily conserved across different enzyme families and its presence is ubiquitous across prokaryotes and eukaryotes.[3]
Use in research
[edit]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]
References
[edit]- ^ Wang, W; Kappock, T J; Stubbe, J; Ealick, S E (1998-11-01). "X-ray crystal structure of glycinamide ribonucleotide synthetase from Escherichia coli". Biochemistry. 37 (45): 15647–15662. doi:10.1021/bi981405n. ISSN 1520-4995. PMID 9843369.
- ^ Eroglu, Binnur; Powers-Lee, Susan G (2002-11-01). "Mutational analysis of ATP-grasp residues in the two ATP sites of Saccharomyces cerevisiae carbamoyl phosphate synthetase". Archives of biochemistry and biophysics. 407 (1): 1–9. doi:10.1016/s0003-9861(02)00510-6. ISSN 1096-0384. PMID 12392708.
- ^ a b c "The ATP-grasp enzymes". europepmc.org. 2011. PMC 3243065. PMID 21920581. Retrieved 2024-09-19.
- ^ "The ATP-grasp enzymes". europepmc.org. 2011. PMC 3243065. PMID 21920581. Retrieved 2024-09-19.
- ^ "A diverse superfamily of enzymes with ATP-dependent carboxylate-amine/thiol ligase activity". europepmc.org. 1997. PMC 2143612. PMID 9416615. Retrieved 2024-09-19.