active site
Summary
The active site is the pocket or cleft on an enzyme where the substrate binds and the reaction is catalyzed. Its shape and chemistry match the substrate (lock-and-key or induced fit). Competitive inhibitors bind here, and denaturation that distorts it reduces activity.
Detail
Meaning: The active site is a small region of an enzyme, built by the folded tertiary structure, where substrate binds and chemistry occurs. Side chains there orient the substrate, stabilize the transition state, and sometimes take part directly in the reaction, which lowers activation energy. Specificity comes from the site's shape, charge, and polarity. Two models describe binding: lock-and-key (a rigid, complementary fit) and induced fit (the site adjusts as substrate binds). Induced fit is the more widely accepted account.
On the MCAT: A passage may describe a mutation of an active-site residue and ask how activity changes. Competitive inhibitors bind the active site, so they raise apparent Km and leave Vmax unchanged, and extra substrate can overcome them. Inhibitors that bind elsewhere (noncompetitive) lower Vmax. Heat or extreme pH can denature the enzyme, distort the site, and cut activity. Questions may also ask which residues (acidic, basic, polar) suit a given reaction.
Common confusion: The active site is not the same as an allosteric site. An allosteric site is a separate location where a regulator binds and shifts the enzyme's conformation and activity. Also, a mutation far from the active site can still disrupt it by changing how the protein folds.
Sources
- Lehninger Principles of Biochemistry
- Biochemistry (Berg, Tymoczko, Gatto, Stryer)
- Campbell Biology
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.