Shannon Rufus

Structure of an Amino Acid#

Each amino acid has a common structure:

1
        NH₂
2
         |
3
    H — C — COOH
4
         |
5
         R

• Amine group (-NH₂) - Basic
• Carboxyl group (-COOH) - Acidic
• Hydrogen atom (-H)
• R group (side chain) - Variable, determines the amino acid’s properties

Types of Amino Acids#

Based on their R groups, amino acids can be:

TIP

The properties of amino acid side chains determine how proteins fold and interact with other molecules.

Primary Structure#

The primary structure is the specific sequence of amino acids in a polypeptide chain, joined by peptide bonds.

1
Peptide bond formation (condensation reaction):
2
    H₂N—CH(R)—COOH + H₂N—CH(R)—COOH →
3
    H₂N—CH(R)—CO—NH—CH(R)—COOH + H₂O

IMPORTANT

The primary structure is determined by DNA and dictates all higher levels of structure. A single change (mutation) can dramatically affect protein function.

Example: Sickle cell anaemia is caused by a single amino acid substitution (glutamic acid → valine) in the haemoglobin beta chain.

Secondary Structure#

The polypeptide chain folds into regular patterns due to hydrogen bonding between the carbonyl oxygen of one amino acid and the amine hydrogen of another.

1
α-Helix:              β-Pleated Sheet:
2
    ↻↻↻↻                ↑↑↑↑↑↑↑↑
3
   ↻ ↻ ↻ ↻              ||||||||
4
    ↻↻↻↻                ↓↓↓↓↓↓↓↓

Tertiary Structure#

The 3D folding of a polypeptide chain into a compact, globular shape. Stabilised by various interactions:

NOTE

Disulfide bridges (between cysteine residues) are particularly important for stabilising extracellular proteins like antibodies.

Quaternary Structure#

Some proteins consist of multiple polypeptide chains (subunits) held together by the same interactions as tertiary structure.

Examples:

• Haemoglobin - 4 subunits (2α + 2β chains, each with a haem group)
• Collagen - Triple helix of 3 polypeptide chains
• Antibodies - 4 chains (2 heavy + 2 light)

Not all proteins have quaternary structure - some are functional as single polypeptide chains.

Key Properties#

1. Specificity - Each enzyme catalyses one specific reaction (or type of reaction)
2. Temperature sensitivity - Rate increases with temperature up to an optimum, then declines
3. pH sensitivity - Each enzyme has an optimal pH
4. Concentration effect - Rate increases with enzyme/substrate concentration (up to a point)

The Lock and Key Model#

Traditional model proposed by Emil Fischer (1894):

• Active site is rigid and precisely shaped
• Substrate fits like a key in a lock
• Explains enzyme specificity but not flexibility

1
    Enzyme           Substrate         ES Complex
2
   ┌─────┐           ◯                  ┌─────┐
3
   │ ╳   │    +        →      →        │  ◯  │
4
   └─────┘                             └─────┘
5
   (Active site)                      (Enzyme-Substrate)

The Induced Fit Model#

Modern model (Daniel Koshland, 1958):

• Active site is flexible
• Substrate binding induces conformational change
• This change:
  • Brings catalytic groups into position
  • Puts strain on substrate bonds
  • Lowers activation energy

TIP

Think of it like a hand gripping a ball - the hand shape changes slightly to accommodate the object!

Temperature#

1
Reaction Rate
2
      |
3
      |        ╭─────
4
      |       ╱
5
      |      ╱
6
      |     ╱
7
      |    ╱
8
      |___╱_________ Temperature
9
          Optimum

• Below optimum: Increased kinetic energy, more collisions
• At optimum: Maximum rate
• Above optimum: Enzyme denatures - hydrogen bonds break, 3D shape lost, active site changes

pH#

Each enzyme has an optimal pH where its 3D structure is most stable.

Changes in pH alter ionisation of R groups, affecting ionic bonds and hydrogen bonding → denaturation.

Substrate Concentration#

1
Rate
2
   |
3
   |        ──────── (Vmax - maximum rate)
4
   |       ╱
5
   |      ╱
6
   |     ╱
7
   |    ╱
8
   |___╱__________ Substrate concentration

• Increasing substrate increases rate (more collisions)
• Eventually plateaus at Vmax - all active sites occupied
• Michaelis constant (Km) = substrate concentration at ½ Vmax

Enzyme Concentration#

More enzyme = more active sites = faster reaction (assuming substrate is not limiting).

Enzyme Inhibitors#

Practice Questions#

1. Explain how a mutation changing one amino acid could affect enzyme function.

2. Describe and explain the effect of increasing temperature on enzyme activity above the optimum.