Allosteric Enzyme - Kinetic Properties

Kinetic Properties

Hemoglobin is the canonical example of an allosteric enzyme - and one of the earliest to have its crystal structure solved (by Max Perutz). More recently, the E. coli enzyme aspartate carbamoyltransferase (ATCase) has become another good example of allosteric regulation.

The kinetic properties of allosteric enzymes are often explained in terms of a conformational change between a low-activity, low-affinity "tense" or T state and a high-activity, high-affinity "relaxed" or R state. These structurally distinct enzyme forms have been shown to exist in several known allosteric enzymes.

However the molecular basis for conversion between the two states is not well understood. Two main models have been proposed to describe this mechanism: the "concerted model" of Monod, Wyman, and Changeux,, and the "sequential model" of Koshland, Nemethy, and Filmer.

In the concerted model, the protein is thought to have two “all-or-none” global states. This model is supported by positive cooperativity where binding of one ligand increases the ability of the enzyme to bind to more ligands. The model is not supported by negative co operativity where losing one ligand make it easier for the enzyme to lose more.

In the sequential model there are many different global conformational/energy states. Binding of one ligand changes the enzyme so it can bind more ligands more easily i.e. every time it binds a ligand it wants to bind another one.

Neither model fully explains allosteric binding, however. The recent combined use of physical techniques (for example, x-ray crystallography and solution small angle x-ray scattering or SAXS) and genetic techniques (site-directed mutagenesis or SDM) may improve our understanding of allostery.