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ATP-grasp

From Wikipedia, the free encyclopedia
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
SymbolATP-grasp
PfamPF02222
Pfam clanCL0179
ECOD206.1.3
InterProIPR013815
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

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

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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

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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

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Evolution and distribution

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

Use in research

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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

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  1. ^ Wang W, Kappock TJ, Stubbe J, Ealick SE (November 1998). "X-ray crystal structure of glycinamide ribonucleotide synthetase from Escherichia coli". Biochemistry. 37 (45): 15647–15662. doi:10.1021/bi981405n. PMID 9843369.
  2. ^ Eroglu B, Powers-Lee SG (November 2002). "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. PMID 12392708.
  3. ^ a b c d Fawaz MV, Topper ME, Firestine SM (December 2011). "The ATP-grasp enzymes". Bioorganic Chemistry. 39 (5–6): 185–191. doi:10.1016/j.bioorg.2011.08.004. PMC 3243065. PMID 21920581.
  4. ^ Galperin MY, Koonin EV (December 1997). "A diverse superfamily of enzymes with ATP-dependent carboxylate-amine/thiol ligase activity". Protein Science. 6 (12): 2639–2643. doi:10.1002/pro.5560061218. PMC 2143612. PMID 9416615.
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