Cysteine (Cys, C) - Structure, pKa, pI, and Codons

Side chain

The R group of cysteine is -CH₂SH. Thiomethyl; a thiol. 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

Cysteine has 3 ionizable groups: alpha-COOH (pKa 1.96), side chain thiol (pKa 8.18), alpha-NH3+ (pKa 10.28). 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 = (1.96 + 8.18) / 2 = 5.07

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-cysteine is (R). The one L-amino acid that is (R). The side chain carbon carries (S,H,H) and sulfur (Z=16) outranks the carboxyl carbon's (O,O,O) at the first point of difference, swapping CIP priorities 2 and 3. The spatial arrangement is still L - only the descriptor changes. Methionine is still (S) because its sulfur sits two bonds out and is never reached before the decision is made.

Genetic code

2 codons encode cysteine: UGU, UGC.

Features

• Sulfur-containing
• Forms disulfide bonds

MCAT notes

• The one L-amino acid that is (R) - a CIP naming quirk, not a change in spatial arrangement.
• Its thiol pKa is 8.18, unusually acidic for the set: about 6% ionized at pH 7.0.
• Forms disulfide bonds - covalent cross-links - with another cysteine to give cystine. Reversed by reducing agents such as DTT or beta-mercaptoethanol.
• Found mostly in extracellular and secreted proteins, because the cytosol is a reducing environment.
• Its thiol deprotonates before the alpha-amino group, so its pI uses pKa1 and pKaR rather than pKa1 and pKa2.

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