ATP-dependent enzymes

ATP-dependent enzymes represent a vast and diverse class of proteins that utilize the energy derived from adenosine triphosphate (ATP) hydrolysis to catalyze essential biochemical reactions (NIH, 2023). This category encompasses several major functional groups, including kinases, which transfer phosphate groups to substrates; ATPases, which drive ion transport and mechanical work; and ligases, which join molecules together (Khan Academy, 2023). These enzymes are fundamental to nearly every cellular process, ranging from signal transduction and metabolic regulation to DNA replication and protein folding (UniProt, 2024). Due to their central roles in cellular homeostasis, dysregulation of ATP-dependent enzymes is a hallmark of numerous pathologies, including oncogenesis, neurodegeneration, and metabolic syndromes (Nature Reviews Drug Discovery, 2002). In the context of drug discovery, ATP-dependent enzymes are among the most successful therapeutic targets, particularly within the kinase and ATPase subfamilies (PubMed, 2021). Small-molecule inhibitors often target the highly conserved ATP-binding pocket to block enzymatic activity, though this approach necessitates high selectivity to avoid off-target interactions with other members of the ATP-utilizing proteome (Tocris Bioscience, 2024). Notable examples of drugs targeting this class include tyrosine kinase inhibitors for cancer and proton pump inhibitors for gastric disorders (StatPearls, 2023). However, the ubiquity of ATP-binding motifs across thousands of human proteins presents significant challenges in achieving the desired safety profile and avoiding systemic toxicity (NIH, 2021).

Other names

ATP-utilizing enzymesATPasesKinasesPhosphotransferasesNucleotide-dependent enzymes

Competitive inhibition of the ATP-binding pocket, allosteric inhibition, or covalent modification to prevent ATP hydrolysis or phosphate group transfer.