Biochemistry: Amino Acids and Peptide Bonds

Protein Structure and Function

• Proteins perform various biological functions, including structural, movement, enzymatic, transport, membrane transport, hormonal, receptor, defense, and gene regulation.
• Examples of proteins and their functions:
  • Structural: collagen, keratin
  • Movement: actin, myosin
  • Enzymes: trypsin, DNA polymerase
  • Transport: haemoglobin, transferrin
  • Membrane transport: Na+/K+ pump
  • Hormones: insulin
  • Receptors: acetyl choline receptor
  • Defence: antibodies, clotting factors
  • Gene regulation: histones
  • Chromosome separation: tubulin

Amino Acids and Polypeptides

• Amino acids have a specific structure, with a NH3+ group at the N-terminal end and a COO- group at the C-terminal end.
• Amino acid side chains can form various interactions, including hydrogen bonds, ionic, van der Waals, and hydrophobic interactions.
• Disulphide (S-S) bridges can form between two cysteine residues, joining subunits together (e.g., insulin).
• Glycosylation can occur, with O-linked and N-linked modifications.

Protein Structure

• 3D structure has four levels: primary, secondary, tertiary, and quaternary.
• Primary structure: sequence of amino acids in the peptide chain.
• Secondary structure: folding/coiling of the peptide chain, often into α-helix or β-pleated sheet.
• Tertiary structure: peptide chain folds upon itself, forming a 3D structure.
• Quaternary structure: folded peptide chains join together to form a functional protein.

α-Helix

• Formed by hydrogen bonds between peptide bonds in the same polypeptide chain.
• Hydrogen bonds formed between peptide bond carbonyl-O and H of N-H every 4th peptide.
• Regular right-handed helix, with 3.6 residues per turn, stabilized by hydrogen bonds.
• R groups on the outside, forming a rigid cylinder shape that provides architectural support for the protein.

β-Pleated Sheets

• Linear peptide chains held together by hydrogen bonds between peptide chains.
• Side chains in each strand alternate above and below the plane of the sheet.
• Antiparallel and parallel β sheet structures exist.

Collagen Triple Helix

• Three chains held together by hydrogen bonds between chains.
• Found in collagen, with a left-handed helix and 3 residues per turn.
• Gly-X-Y-Gly-X-Y-Gly sequence, with X mainly proline and Y mainly hydroxy-proline.

Tertiary and Quaternary Structure

• Tertiary structure: how the whole polypeptide (subunit) is folded in 3D, consisting of different supersecondary structures (domains).
• Quaternary structure: how the whole functional protein is formed in 3D, possibly consisting of multiple subunits (e.g., haemoglobin α2β2).

Forces that Stabilize Protein Structure

• Covalent: disulphide bridges.
• Non-covalent: hydrogen bonds, electrostatic interactions, van der Waals forces, and the hydrophobic effect.

Hydrogen Bonds

• Formed between two electronegative atoms competing for the same H atom.
• Hydrogen bond donors (D): O, N, and NH3+.
• Hydrogen bond acceptors (A): O, N, and =N-.

Electrostatic Interactions

• Between charged side chains: Asp/Glu carboxyl groups (COO-) and Lys/Arg amino groups (NH3+).

Van der Waals Forces

• The sum of attractive or repulsive forces between molecules, excluding covalent bonds, hydrogen bonds, and electrostatic interactions.
• Dependent on dipole effects caused by the unequal distribution of electrons.

Hydrophobic Effects

• Hydrophobic regions of a protein fold to minimize contact with the aqueous environment, unable to form hydrogen bonds.

Protein Structure and Folding

• The amount of stabilization energy in a protein is quite small, making them sensitive to denaturation by pH, temperature, and ionic strength.
• Amino acid sequence encodes the final structure and the pathway that leads to that structure.
• Misfolding can cause disease.