Amino Acids and Protein Structure

Amino Acids:
  - Molecules with four groups attached to a central (α) carbon:
    - Amino group (–NH₂)
    - Carboxylic acid group (–COOH)
    - Hydrogen atom (–H)
    - R Group (side chain which determines function of the amino acid)
  - Stereochemistry:
    - The stereochemistry of the α-carbon is L for all chiral amino acids in eukaryotes (while carbohydrates are D-config).
    - All chiral amino acids, except cysteine, have (S) configuration, while all amino acids are chiral except for Glycine.
Hydrophobic & Hydrophilic:
  - Amino acids with long alkyl chains are hydrophobic.
  - Those with charges are hydrophilic.
  - All others fall somewhere in between.

Amphoteric:
- Amino acids can act as either a base or an acid.
pKa:
- The pH at which half of the species is deprotonated;
- At this pH, [HA] = [A-].
pH Behavior:
  - ↓pH: Amino acid is fully protonated.
  - pH ≈ pI: Amino acid is a neutral zwitterion.
  - ↑pH: Amino acid is fully deprotonated.
Isoelectric Point (pI):
- The pH at which an amino acid is in zwitterion form, where the charges cancel out to make a neutral molecule.

Equations:
  - pKa1 = carboxyl group
  - pKa2 = amine group
  - pKa3 = side chain
For a NEUTRAL side chain:
- $pI = \frac{1}{2} (pKa1 + pKa2)$
For a BASIC side chain:
- $pI = \frac{1}{2} (pKa2 + pKa3)$
For an ACIDIC side chain:
- $pI = \frac{1}{2} (pKa1 + pKa3)$
Titration Key Points:
- Midpoint: $pH = pKa$
- Equivalence Point: $pH = pI$

Terminology:
  - Dipeptide: 2 residues
  - Tripeptide: 3 residues
  - Oligopeptides: Less than 20 residues
  - Polypeptides: Greater than 20 residues
Peptide Bond Formation:
- Forming a peptide bond is a dehydration reaction.
- The nucleophilic amino group of one amino acid attacks the electrophilic carbonyl group of another amino acid.
Amide Bonds:
- The C-N bond of a peptide bond.
- Rigid due to resonance.
Peptide Bond Breaking:
- Breaking a peptide bond is a hydrolysis reaction.

1° Protein Structure:
  - Linear sequence of amino acids in a peptide.
  - Stabilized by peptide bonds.
  - The amino acid sequence is written from N-terminus to C-terminus.
  - N-terminus is POSITIVELY charged due to –NH₃⁺.
2° Protein Structure:
  - The local structure of neighboring amino acids.
  - Stabilized by hydrogen bonding between amino groups and non-adjacent carboxyl groups.
  - α-helices:
    - A common 2° structure; clockwise coils around a central axis.
  - β-pleated sheets:
    - A common 2° structure; rippled strands can be parallel or antiparallel.
  - Proline:
    - Can interrupt 2° structure because of its rigid cyclic structure.

3° Protein Structure:
- Three-dimensional folding pattern of a protein due to side chain interactions.
4° Protein Structure:
- Protein consisting of more than one amino acid chain.
Denaturation:
  - When a protein (or nucleic acid) loses its 4°, 3°, and 2° structures due to breaking non-covalent interactions such as:
    - Hydrogen bonds
    - Hydrophobic interactions
    - Dipole-dipole interactions
3° Structure Stabilization:
  - 3-D shape of a single polypeptide chain, stabilized by:
    - Hydrophobic interactions
      - Push hydrophobic R groups to the interior of a protein, which increases entropy of the surrounding water molecules and creates a negative Gibbs free energy.
    - Disulfide Bonds: Occur when two cysteine molecules are oxidized, creating a covalent bond between their thiol groups, forming cystine.
4° Structure:
- The interaction between peptides in proteins that contain multiple subunits.

Conjugated Proteins:
- Proteins with covalently attached molecules.
Prosthetic Group:
  - The attached molecule in a conjugated protein, which can include:
    - Metal ions
    - Vitamins
    - Lipids
    - Carbohydrates
    - Nucleic acids
Denaturation:
  - The loss of 3-D structure, typically caused by:
    - Changes in heat
    - Alterations in solute concentration.