Histidine (His, H) - Structure, pKa, pI, and Codons

Side chain

The R group of histidine is -CH₂-imidazole. Imidazol-4-ylmethyl; an aromatic five-membered ring with two nitrogens. This is what distinguishes it from the other 19 amino acids, since all of them share the same backbone: an alpha carbon bonded to an amino group, a carboxyl group, and a hydrogen.

Ionization and isoelectric point

Histidine has 3 ionizable groups: alpha-COOH (pKa 1.82), side chain imidazole (pKa 6.00), alpha-NH3+ (pKa 9.17). The isoelectric point is the pH at which the molecule carries no net charge, found by averaging the two pKa values that bracket the neutral species.

pI = (9.17 + 6) / 2 = 7.59

Note that this uses the side chain pKa rather than both alpha group values, because the side chain ionizes within the range that brackets the neutral form.

These values are for the free amino acid. Inside a folded protein, the local environment shifts them substantially.

Stereochemistry

The alpha carbon of L-histidine is (S).

Genetic code

2 codons encode histidine: CAU, CAC.

MCAT notes

• The only side chain with a pKa near physiological pH (6.00), which makes it the dominant protein buffer at pH 7.4.
• The residue of choice for general acid-base catalysis, since it can both donate and accept a proton at physiological pH.
• Found in the serine protease catalytic triad, in carbonic anhydrase coordinating zinc, and in hemoglobin coordinating heme iron - the Bohr effect relies on its protonation.
• Trap: at pH 7.4 histidine is only about 4% protonated. It is called basic because it can protonate near physiological pH, not because it usually is.
• Aromatic as well as basic - both classifications are defensible.

Related Topics