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 (or A-domain), the central domain (or B-domain), and the C-terminal domain (or C-domain).

Function

ATP-grasp enzymes

catalyse Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...

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 Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms. Biosynthesis Purines are biologically synthesized as nucleotides and in particular as ribotides, i.e. bases attached to ...

fatty acid synthesis In biochemistry, fatty acid synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes. Two ''De novo synthesis, de novo'' fatty acid syntheses can be distinguished: cytosolic fatty acid synthesis (FAS/FASI) ...

, and

gluconeogenesis Gluconeogenesis (GNG) is a metabolic pathway that results in the biosynthesis of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In verte ...

Examples of proteins containing this domain

* D-alanine-D-alanine ligase *

glutathione synthetase Glutathione synthetase (GSS) () is the second enzyme in the glutathione (GSH) biosynthesis pathway. It catalyses the condensation of gamma-glutamylcysteine and glycine, to form glutathione. Glutathione synthetase is also a potent antioxidan ...

biotin carboxylase In enzymology, a biotin carboxylase () is an enzyme that catalyzes the chemical reaction : ATP + biotin-carboxyl-carrier protein + CO2 \rightleftharpoons ADP + phosphate + carboxybiotin-carboxyl-carrier protein The three substrates of this e ...

carbamoyl phosphate synthetase Carbamoyl phosphate synthetase catalyzes the ATP-dependent synthesis of carbamoyl phosphate from glutamine () or ammonia () and bicarbonate. This ATP-grasp enzyme catalyzes the reaction of Adenosine triphosphate, ATP and bicarbonate to produc ...

* ribosomal protein S6 modification enzyme (RimK) *

urea Urea, also called carbamide (because it is a diamide of carbonic acid), is an organic compound with chemical formula . This amide has two Amine, amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest am ...

amidolyase * tubulin-tyrosine ligase * enzymes involved in

Evolution and distribution

The ATP-grasp fold is evolutionarily conserved across different

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

families Family (from ) is a group of people related either by consanguinity (by recognized birth) or affinity (by marriage or other relationship). It forms the basis for social order. Ideally, families offer predictability, structure, and safety as ...

and its presence is ubiquitous across

prokaryotes A prokaryote (; less commonly spelled procaryote) is a single-celled organism whose cell lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Greek (), meaning 'before', and (), meaning 'nut' ...

and

eukaryotes The eukaryotes ( ) constitute the domain of Eukaryota or Eukarya, organisms whose cells have a membrane-bound nucleus. All animals, plants, fungi, seaweeds, and many unicellular organisms are eukaryotes. They constitute a major group of ...

Use in research

Researchers have developed several types of inhibitors for these

enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...

, including mechanism-based inhibitors, ATP-competitive inhibitors, and non-competitive inhibitors. Some ATP-grasp enzymes are being studied as potential targets for

antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

and

anti-obesity drugs Anti-obesity medication or weight loss medications are pharmacological agents that reduce or control excess body fat. These medications alter one of the fundamental processes of the human body, weight regulation, by: reducing appetite and con ...

References

{{Reflist

External links

InterPro: ATP-grasp fold, subdomain 1 (IPR013815)

InterPro: ATP-grasp fold, subdomain 2 (IPR013816)
Protein domains Protein folds Protein superfamilies