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Life Science Dictionary

Active site

Biochemistry · Pharmacology

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The active site is the pocket or groove on an enzyme where the substrate binds and the chemical reaction is catalyzed.

Also: catalytic site, active centre

Definition

What is the active site?

The active site is the small region of an enzyme that binds its substrate and carries out the reaction. It is usually a cleft or pocket formed as the protein chain folds, so amino acids that lie far apart in the sequence can end up side by side there. The shapes and chemical properties of their side chains, whether charged, polar or water-repelling, create an environment that suits only certain molecules, and this is the source of an enzyme's specificity.

The older lock-and-key model pictured the substrate fitting a rigid active site exactly. The induced-fit model, now preferred, holds that the site changes shape slightly as the substrate binds, gripping it more closely and straining the bonds that need to break. Once the product forms, it is released and the site is free to bind another substrate.

Because the active site depends on the protein's folded shape, heat or extreme pH that denatures an enzyme destroys it. Many drugs are designed to occupy an active site, which is how a competitive inhibitor works, while allosteric regulators bind elsewhere on the enzyme and alter the site's shape from a distance.

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