Histidine

His · H · 155.15 Da

EssentialCharged Essential

Imidazole

Classified basic, but with pKa 6.0 it is only about 4% protonated at pH 7.4, so essentially neutral. That near-neutral pKa is exactly why it is the workhorse acid/base catalyst and the classic metal-coordinating residue.

Mnemonic

H for His, and for the H⁺ it hands back and forth. The only side chain that buffers near pH 7.

Ionization ladder

pKa	Group	Change	Charge
1.82	α-carboxyl	-COOH → -COO⁻	0 → −1
6.00	side chain	protonated → neutral	+1 → 0
9.17	α-amino	-NH₃⁺ → -NH₂	+1 → 0

pI = (6.00 + 9.17) / 2 = 7.58, the midpoint of the two pKa values that bracket the neutral species.

Net charge across pH

pH 1+2

pH 4+1

pH 70

pH 10−1

pH 13−1

A group is deprotonated once the pH climbs past its pKa. Add the contributions and you have the net charge, with no memorization required.