The lock and key hypothesis was proposed by Emil Fischer in 1894 to explain how enzymes work and why they are specific.In this model:
• the active site has a fixed, rigid shape
• only a substrate with a shape exactly complementary to the active site can fit into it, just as only the right key fits a lock
• when the substrate fits, an enzyme-substrate complex forms
• the reaction happens and an enzyme-product complex forms
• the products no longer fit, so they are released, leaving the enzyme unchanged and free to bind another substrate
• why enzymes are specific: other molecules have the wrong shape
• why enzymes are reused
• why a change in the shape of the active site (for example by denaturation) stops the enzyme workingLimitations of the model:
• studies of enzyme structure show that the active site is not rigid but changes shape slightly when the substrate binds
• some enzymes, such as lipase, act on a range of similar substrates, which a completely rigid active site cannot explain
• it does not explain how binding lowers the activation energyFor these reasons the lock and key hypothesis has been modified into the induced fit hypothesis.
• the active site has a fixed, rigid shape
• only a substrate with a shape exactly complementary to the active site can fit into it, just as only the right key fits a lock
• when the substrate fits, an enzyme-substrate complex forms
• the reaction happens and an enzyme-product complex forms
• the products no longer fit, so they are released, leaving the enzyme unchanged and free to bind another substrate
• why enzymes are specific: other molecules have the wrong shape
• why enzymes are reused
• why a change in the shape of the active site (for example by denaturation) stops the enzyme workingLimitations of the model:
• studies of enzyme structure show that the active site is not rigid but changes shape slightly when the substrate binds
• some enzymes, such as lipase, act on a range of similar substrates, which a completely rigid active site cannot explain
• it does not explain how binding lowers the activation energyFor these reasons the lock and key hypothesis has been modified into the induced fit hypothesis.