Histidine is one of the 20 ribosomally encoded protein amino acids. It was first isolated by the German physician and biochemist Albrecht Kossel in 1896. It is distinguished by having a side chain with an imidazole ring, which has a pKa of approximately 6. Histidine has an isoelectric point (pI) of 7.6; thus, at typical intracellular pH values, relatively small shifts in pH can greatly change its average charge. When protonated, the imidazole ring is positively charged, with the positive charge distributed between both ring nitrogen atoms, which can be represented by two resonance structures. The imidazole ring of histidine is aromatic at all pH values as it contains six π electrons, is a common coordinating ligand in metalloproteins, and is a part of the catalytic sites of many enzymes.
Histidine has not been identified in carbonaceous chondrites and is difficult to be formed in Miller-type prebiotic synthesis experiments, while imidazole can be easily obtained in them.