Histidine residue (His)

A **histidine residue** refers to the amino acid histidine when incorporated as a side chain into a polypeptide or protein. Histidine (abbreviated **His** or **H**) is one of the 20 standard proteinogenic amino acids. It is unique for its imidazole side chain, which has a pKa close to physiological pH, allowing the residue to act efficiently as both a proton donor and acceptor under biological conditions. This dual acid-base capability is critical for enzyme active sites, protein folding, and stabilization via hydrogen bonds and metal ion coordination. Histidine residues are highly versatile in mediating molecular interactions, including π–π stacking, cation–π interactions, and direct binding to metal ions such as Zn²⁺ or Ca²⁺, and serve as sites for diverse posttranslational modifications including phosphorylation and methylation[2][3][4][5][6]. Histidine residues do not represent a molecular target, receptor, enzyme, or transporter in isolation, but are structural and functional components of various proteins that may themselves be drug targets. Individual histidine residues are not directly targeted by drugs or considered biomarkers or therapeutic targets, though histidine-rich sites may modulate the function of drug-binding proteins or enzymes[5]. The entry "histidine residue" is typically not considered a discrete drug target but rather a biochemical descriptor of an amino acid position or motif within a protein.

Other names

HistidineHisHL-histidine residue