nucleotidebinding

Nucleotide-binding refers to the interaction between a molecule, most often a protein, and nucleotides such as ATP, GTP, NAD+, or other ribonucleotides. In biology, nucleotide binding is central to energy transduction, metabolic cofactors, and regulatory signaling. Proteins that bind nucleotides may use the bound nucleotide as an energy source for catalysis, as a substrate for transfer reactions, or as a molecular switch that controls activity in response to nucleotide state.

Many nucleotide-binding proteins share conserved structural motifs that recognize the nucleotide’s phosphate groups and its adenine or nicotinamide ring. A common class is the P-loop NTPases, which feature the Walker A motif (GxxxxGKT/S) and a Walker B motif that coordinates Mg2+. Another widespread fold is the Rossmann fold, which binds dinucleotides such as NAD+/NADH. Nucleotide-binding domains are found in diverse proteins, including ATP-binding cassette transporters, kinases that transfer phosphate from ATP, and GTPases such as Ras and tubulin that act as molecular switches. Additional proteins bind deoxynucleotides or other nucleotides for catalytic or redox roles.

Binding interactions are typically studied by measuring affinity (Kd), thermodynamics (ITC), or kinetics (SPR), and by structural methods such as X-ray crystallography or NMR. Disruption or modulation of nucleotide binding can significantly affect activity, making nucleotide-binding sites important targets in pharmacology and disease research. Overall, nucleotide binding is a fundamental mechanism by which cells regulate energy, metabolism, and signaling.