Drug-enzyme interaction

Two Chemically Distinct Modes of Enzyme Inhibition

A drug can interfere with an enzyme's activity by acting as an inhibitor, and there are two chemically distinct ways this can happen:

• Competitive inhibition. The drug molecule is structurally similar enough to the natural substrate that it can physically occupy the same active site, directly competing with the substrate for that space. Once the drug is bound there, the true substrate is excluded and the normal reaction cannot proceed. Figure 16.2's cover art depicts exactly this competition - a drug and a substrate both approaching the same active-site notch, followed by the drug winning that competition and blocking the site outright.
• Non-competitive inhibition. Here the drug does not go anywhere near the active site at all. Instead it binds at a separate, distinct location on the enzyme called the allosteric site. This binding event distorts the overall three-dimensional shape of the enzyme, which in turn changes the shape of the active site itself - so that the substrate can no longer be recognised or bound there, even though the active site is physically unoccupied by the drug. Figure 16.3's cover art shows this shape-change explicitly: the active site is redrawn as a flattened, altered groove once the inhibitor has taken up residence at the separate allosteric notch. …