Mechanism-based inhibition: Higher Level only: This statement is Higher Level only. Learn penicillin and transpeptidase, and how a changed transpeptidase makes bacteria resistant.
Practise this as you read
- Explain mechanism-based inhibition.
- Outline how bacteria become resistant to penicillin.
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The big idea: In mechanism-based inhibition, an inhibitor binds to the active site and then chemically changes it. The binding is irreversible, so the enzyme never works again.
The points to remember
- Transpeptidase makes the cross-links that hold a bacterial cell wall together.
- Penicillin binds to its active site and forms a permanent covalent bond with it.
- Without cross-links the wall is weak, so growing bacteria burst.
- Resistant bacteria make a changed transpeptidase whose active site penicillin cannot bind.
Remember it as: Bind, react, finished: the enzyme is out of action for good.
Real example: MRSA. Methicillin-resistant Staphylococcus aureus has a changed transpeptidase that penicillin-type antibiotics bind very poorly, so it keeps building its cell wall.
Trap: Penicillin is not a competitive inhibitor: adding more substrate cannot undo it, because the enzyme has been chemically changed.
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How it is asked: Expect penicillin as the example, how the inhibition differs from reversible inhibition, and how bacteria become resistant.
IB-style questionExplain[3 marks]
Explain how penicillin kills bacteria by mechanism-based inhibition.
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