Enzyme inhibitor
HIV protease in a complex with the protease
inhibitor ritonavir. The structure of the pro-
tease is shown by the red, blue and yellow
ribbons. The inhibitor is shown as the smaller
ball-and-stick structure near the centre.
Created from PDB 1HXW.
Enzyme inhibitors are molecules that bind
to enzymes and decrease their activity. Since
blocking an enzyme’s activity can kill a
pathogen or correct a metabolic imbalance,
many drugs are enzyme inhibitors. They are
also used as herbicides and pesticides. Not
all molecules that bind to enzymes are inhib-
itors; enzyme activators bind to enzymes and
increase their enzymatic activity.
The binding of an inhibitor can stop a sub-
strate from entering the enzyme’s active site
and/or hinder the enzyme from catalysing its
reaction. Inhibitor binding is either reversible
or irreversible. Irreversible inhibitors usually
react with the enzyme and change it chemic-
ally. These inhibitors modify key amino acid
residues needed for enzymatic activity. In
contrast, reversible inhibitors bind non-cova-
lently and different types of inhibition are
produced depending on whether these inhib-
itors bind the enzyme, the enzyme-substrate
complex, or both.
Many drug molecules are enzyme inhibit-
ors, so their discovery and improvement is an
active area of research in biochemistry and
pharmacology. A medicinal enzyme inhibitor
is often judged by its specificity (its lack of
binding to other proteins) and its potency (its
dissociation constant, which indicates the
concentration needed to inhibit the enzyme).
A high specificity and potency ensure that a
drug will have few side effects and thus low
toxicity.
Enzyme inhibitors also occur naturally and
are involved in the regulation of metabolism.
For example, enzymes in a metabolic path-
way can be
inhibited by downstream
products. This type of negative feedback
slows flux through a pathway when the
products begin to build up and is an import-
ant way to maintain homeostasis in a cell.
Other cellular enzyme inhibitors are proteins
th