A drug that is an irreversible inhibitor will bind

Question

BlackTom AI · Accepted Answer

Irreversible inhibitors form a covalent (or otherwise essentially permanent) bond with an enzyme’s functional group, most often targeting catalytic residues in the active site. This permanently inactivates that enzyme molecule until it is degraded and replaced.

Relevant knowledge points:
- “Irreversible” implies a stable, often covalent modification rather than transient weak binding.
- The active site contains residues directly responsible for substrate binding and catalysis (e.g., Ser, Cys, His). Modifying these residues abolishes activity.
- Examples: aspirin acetylates a serine in cyclooxygenase; penicillin acylates the active-site serine of transpeptidase; organophosphates phosphorylate the serine in acetylcholinesterase.
- A subset called “mechanism-based” or “suicide” inhibitors are activated by the enzyme and then form the irreversible bond, but this is a special case — not required for all irreversible inhibitors.

Step-by-step reasoning:
1. Define irreversible inhibitor: binds in a way that cannot be reversed under physiological conditions (usually covalent attachment to enzyme).
2. Identify the most effective place to abolish catalysis: the active site, because modifying catalytic residues directly prevents substrate turnover.
3. Consider molecular mechanism: an electrophilic inhibitor reacts with a nucleophilic side chain (e.g., Ser-OH → acylation), resulting in permanent loss of activity.
4. Conclude that the inhibitor therefore binds at/targets the active site (or residues that play the same catalytic role), consistent with the irreversible effect.

Why other choices are incorrect:
- “Only when the substrate is bound”: describes mechanism-based/suicide inhibitors specifically; not all irreversible inhibitors require substrate presence.
- “At the allosteric site”: allosteric inhibitors typically change conformation and are usually reversible; irreversible modification at allosteric sites is not the general rule.
- “By weak interactions”: weak (noncovalent) interactions characterize reversible inhibitors, not irreversible ones.
- “Only at a site where the prosthetic group is attached”: too restrictive; irreversible inhibitors more commonly target catalytic residues in the active site, not exclusively prosthetic-group linkages.

Therefore the correct answer is: At the active site. This matches the provided answer.

A drug that is an irreversible inhibitor will bind单项选择题

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