Grade 12

Amino acids, peptides, protein structure

Amino acids join through peptide bonds into chains that fold into proteins; four levels of structure explain how sequence determines shape and function.

1 Lower secondary 2 Upper secondary 3 Undergraduate 4 Advanced 5 Research

IntuitionIntuition: twenty letters, endless words

Proteins are long words spelled with an alphabet of twenty amino acids. The order of the letters is the sequence; the chain then folds so that some parts sit inside away from water and others on the outside, and the resulting three-dimensional shape lets the protein act as an enzyme, a fibre or a carrier.

A bent chain with side-chain beads on every second residue; drag to rotate. It is a topological sketch only, not a real protein fold.

SchoolSchool level: amino acids and the peptide bond

Definition:

A compound $\ce{H2N-CHR-COOH}$ with the amino group on the carbon next to the carboxyl group. Twenty different R groups (side chains) occur in proteins; all except glycine are chiral, and natural proteins use the L-form.

\ce{H2N-CHR-COOH + H2N-CHR'-COOH -> H2N-CHR-CO-NH-CHR'-COOH + H2O}

Joining two amino acids removes water and forms an amide called a peptide bond. Two units give a dipeptide, three a tripeptide, and long chains are polypeptides. A peptide with n different amino acids can be arranged in many orders; each end is different (N-terminus with free $\ce{NH2}$ , C-terminus with free $\ce{COOH}$ ).

Example: How many tripeptides?

Three different amino acids (Gly, Ala, Val) each used once: how many distinct tripeptides can form? How many if each position may be any of the three?

Solution

Each used once: 3! = 6 orderings, because order matters (Gly-Ala-Val differs from Val-Ala-Gly). With repetition allowed: 3³ = 27.

UndergraduateUniversity: ionization and the four levels of structure

In water an amino acid is a zwitterion, $\ce{^+H3N-CHR-COO-}$ . Its net charge is zero at the isoelectric point pI, which for a neutral amino acid is the average of the two pKa values (glycine: pKa 2.34 and 9.60, so pI ≈ 5.97). The peptide bond has partial double-bond character, so the six atoms around it are planar and usually trans.

\mathrm{pI}=\tfrac12\left(\mathrm{p}K_{a1}+\mathrm{p}K_{a2}\right)

Levels of protein structure
Level	What it is	Main stabilizing forces
Primary	Amino-acid sequence	Covalent peptide bonds
Secondary	α-helix, β-sheet	Backbone C=O···H–N hydrogen bonds
Tertiary	Overall 3D fold of one chain	Hydrophobic effect, salt bridges, disulfide bonds
Quaternary	Assembly of several chains	Same non-covalent forces between subunits

Example: Isoelectric point of glycine

Glycine has pKa(COOH) = 2.34 and pKa(NH₃⁺) = 9.60. Find pI and say which way it migrates at pH 8 in an electric field.

Solution

pI = (2.34 + 9.60)/2 = 5.97. At pH 8 > pI the molecule carries a net negative charge (the ammonium is mostly still protonated, but the excess of $\ce{COO-}$ over $\ce{NH3+}$ is small), so it moves slowly toward the positive electrode.

References

Lehninger Principles of Biochemistry (8th ed.) · David L. Nelson, Michael M. Cox, Aaron A. Hoskins, 2021
The Structure of Proteins: Two Hydrogen-Bonded Helical Configurations of the Polypeptide Chain · Linus Pauling, Robert B. Corey, H. R. Branson, 1951