Enzymes – Part II Biochemistry I Lecture 2 2009 (J.S.) Induced-fit model of enzyme-substrate binding: The enzyme changes shape on substrate binding. The active site forms a shape complementary to the substrate only after the substrate has been bound. Irreversible inhibition Irreversible inhibitors are usually compounds not of biological origin, which bind onto an enzyme mostly covalently and make substrate binding impossible. Some of them called "active-site directed inhibitors" are used in experimental studies of enzymes because they permit to map the active sites (affinity labels structurally similar to the substrate, other group-specific reagents). Heavy metal ions bind and inhibit irreversibly enzymes during isolation. Mechanism-based inhibitors (suicide inhibitors) are recognized as substrates, initially processed, but catalysis generates a reactive intermediate that inactivates the enzyme (e.g. α[1]-antitrypsin, penicillin, aspirin).