The induced fit model

The induced fit model of enzyme action says that an enzyme's active site is not exactly the same shape as its substrate to begin with. When the substrate binds, the active site changes shape slightly and moulds itself around the substrate, forming an enzyme-substrate complex. This change puts strain on bonds in the substrate, which lowers the activation energy of the reaction. It replaced the older lock and key model and is the model A-level Biology uses.

What is the induced fit model?

An enzyme is a protein with a specific tertiary structure. One small region of it, the active site, is where the substrate binds. In the induced fit model, the active site and substrate are roughly complementary, but not a perfect match. The binding of the substrate induces a change in the shape of the active site, so that it fits closely around the substrate.

The idea came from the American biochemist Daniel Koshland, who published it in 1958. He argued that the substrate causes a change in the arrangement of the enzyme, which brings the catalytic groups into the right positions. X-ray structures have since shown it happening: the enzyme hexokinase, for example, closes around a glucose molecule when it binds.

The steps of enzyme action by induced fit

1. The substrate collides with the enzyme and enters the active site.
2. The substrate binds, forming an enzyme-substrate complex.
3. The active site changes shape to fit more closely around the substrate.
4. This puts strain on bonds in the substrate, or holds two substrate molecules close together in the right position, so the reaction needs less energy.
5. The reaction happens and an enzyme-product complex forms.
6. The products no longer fit the active site and are released.
7. The active site returns to its original shape, ready for another substrate molecule.

How induced fit lowers activation energy

AQA A-level Biology says each enzyme lowers the activation energy of the reaction it catalyses. Induced fit explains how:

• Breaking a bond: as the active site tightens round the substrate, it bends and stretches bonds in the substrate, making them easier to break.
• Joining two molecules: the active site holds two substrates close together, with the right parts facing each other, so they react more easily than if they had to collide by chance.

Either way, less energy is needed to start the reaction, so more molecules have enough energy to react at body temperature, and the reaction goes much faster.

Induced fit vs lock and key

The lock and key model, put forward much earlier by the German chemist Emil Fischer, pictured the active site as a rigid lock and the substrate as a key of exactly the right shape. It explains specificity well, and GCSE courses still use it. The induced fit model keeps the idea that the shapes must be complementary, but makes the active site flexible.

For a GCSE-level account of enzymes, digestive enzymes and the effect of temperature and pH, see biological catalysts.

Why the induced fit model is better

• It matches the evidence. Structures of enzymes with and without their substrate show the active site changing shape.
• It explains activation energy. A rigid lock could not strain the substrate's bonds.
• It explains non-competitive inhibitors. They bind away from the active site, at an allosteric site, yet still stop the enzyme. That only makes sense if the protein is flexible, so a change in one place alters the shape of the active site.
• It explains why some similar molecules bind but do not react. They fit the active site without causing the right change in shape.

Exam questions with answers

Describe the induced fit model of enzyme action.

The substrate binds to the active site, which is roughly complementary in shape. The active site changes shape slightly to mould around the substrate, forming an enzyme-substrate complex. This puts strain on the substrate's bonds, lowering the activation energy, so the reaction happens. The products are released and the active site returns to its original shape.

Explain why an enzyme only catalyses one reaction.

The active site has a specific shape, set by the enzyme's tertiary structure. Only a substrate with a complementary shape can bind and induce the right change in the active site to form an enzyme-substrate complex. Other molecules cannot bind, or cannot cause the change.

Explain how a high temperature stops an enzyme working.

The extra kinetic energy makes the enzyme vibrate so much that hydrogen bonds and ionic bonds holding its tertiary structure break. The active site loses its shape, so the substrate can no longer bind and no enzyme-substrate complexes form. The enzyme is denatured.

Check your understanding.

Common mistakes

• Saying the substrate changes shape to fit the enzyme. In this model it is the active site that changes. The substrate's bonds are strained, but it is the enzyme that moulds.
• Saying the active site is the same shape as the substrate. Say complementary.
• Saying the change is permanent. The active site returns to its original shape after the products are released; permanent loss of shape is denaturation.
• Forgetting the enzyme-substrate complex. Examiners expect the term.
• Saying enzymes provide energy. They lower the activation energy; they do not supply energy.

Practise with a short timed paper

Enzymes are in the first year of A-level Biology. The daily A-level Biology: Year 1 paper is a short timed paper of 8 questions, with a new one every day.

Read next

Biology · Biological moleculesBiological catalysts are enzymes: how enzymes workBiological catalysts are called enzymes. How enzymes work, the active site and lock and key model, temperature, pH and denaturation, and digestive enzymes.