Question
Explain the lock and key model and induced fit model of enzyme action. How do they differ?
Solution — Step by Step
Enzymes are biological catalysts — proteins that speed up biochemical reactions without being consumed. They work by binding to a specific substrate (the molecule they act on) at a region called the active site. The active site is a three-dimensional pocket or groove on the enzyme’s surface whose shape, size, and chemical properties are complementary to the substrate.
How the enzyme and substrate fit together has been explained by two models.
Proposed by Emil Fischer in 1894, this is the older model. It states:
- The active site of an enzyme has a rigid, fixed shape — like a lock
- The substrate is the key that fits exactly into this rigid lock
- The shape of the active site and the substrate are perfectly complementary before they even meet
- No conformational change occurs in the enzyme when the substrate binds
This model explains specificity (why each enzyme acts on only specific substrates) very well. An enzyme that acts on glucose won’t fit galactose — the “key” doesn’t fit.
Diagram description: Draw the enzyme as a fixed C-shape with a specific pocket. Draw the substrate as a matching shape. Show them fitting together perfectly without any change in the enzyme’s shape.
Proposed by Daniel Koshland in 1958, this model refined the lock and key concept:
- The active site is NOT rigid — it is flexible
- When the substrate approaches the enzyme, the enzyme’s active site changes shape (undergoes conformational change) to accommodate the substrate
- The enzyme is “induced” to adopt the best shape for binding by the substrate itself
- The substrate may also change shape slightly
- The fit becomes optimal only AFTER the substrate starts binding
This is like a hand and glove: the glove has a general shape, but conforms to the exact shape of your hand when you put it on.
Diagram description: Draw the enzyme with a slightly different pocket shape. Draw the substrate approaching. Then show the enzyme changing shape to perfectly embrace the substrate in the second panel.
The induced fit model is now the accepted model. It explains several phenomena the lock and key model cannot:
- How enzyme activity is regulated — inhibitors and activators can bind elsewhere (allosteric sites) and change the shape of the active site
- Competitive and non-competitive inhibition — flexible active sites can accommodate structurally similar molecules
- Why some substrates bind but aren’t converted — the conformational change for catalysis may not occur for all bound molecules
- Enzyme cooperativity — in multi-subunit enzymes, substrate binding at one site induces conformational changes that affect other sites
Comparison Table
| Feature | Lock and Key Model | Induced Fit Model |
|---|---|---|
| Active site | Rigid, fixed | Flexible, changeable |
| Substrate fit | Perfect before binding | Perfected during binding |
| Enzyme change | None | Conformational change |
| Year | 1894 (Fischer) | 1958 (Koshland) |
| Explains specificity | Yes | Yes |
| Explains allostery | No | Yes |
| Explains inhibition | Partially | Fully |
| Current acceptance | Historical | Accepted model |
Why This Works
The induced fit model reflects what we now know about protein structure. Proteins are not rigid machines — they are dynamic molecules that constantly flex and move. Enzyme-substrate interactions involve multiple weak forces (hydrogen bonds, hydrophobic interactions, van der Waals forces). As the substrate approaches, these forces incrementally pull the enzyme into the optimal binding conformation. This “proofreading” during binding actually increases selectivity — the enzyme can discriminate between substrates that would have looked similar in a rigid lock-and-key model.
NEET frequently asks: “Which model better explains enzyme specificity?” Both models explain specificity, but the induced fit model ALSO explains why enzyme activity can be regulated allosterically — this is the key advantage. If the question asks which model is currently accepted, always write “induced fit model.”
Common Mistake
Students sometimes write that the lock and key model says “the enzyme and substrate can fit in multiple ways.” No — that’s the OPPOSITE of the lock and key model. Lock and key is about a single, rigid, specific fit. Another common error is attributing the induced fit model to the wrong scientist. It’s Koshland (1958), not Fischer. Fischer proposed lock and key (1894). CBSE and NEET mark schemes check these attributions.