In biochemistry, a ligand is an effector, a molecule that binds to a site on a macromolecule's surface by intermolecular forces, thereby changing the chemical conformation of the macromolecule. Once a molecule's conformation has changed, its ability to function in other chemical reactions is altered. This binding is usually a reversible reaction, i.e. it can be undone. Actual coordinate covalent bonds between a ligand and its target molecule are rare in biological systems. Ligands include substrates, inhibitors, activators, and neurotransmitters.

Whether or not the ligand actually binds at a metal site is irrelevant, as opposed to 'ligand' in chemical sense. 'Ligand' is probably originally a carryover term from the large number of binding studies on oxygen transport proteins, such as hemoglobin, in which the ligand does indeed bind at a metal site. In the case of hemoglobin oxygen acts as a ligand.

Protein ligands are studied in structural biology and metabolomics. Radioactive ligands (radioligands) are used together with positron emission tomography to study the receptor systems of the brain.

In basic biology, ligands attach to receptors as a way of cytoplasmic signaling in a cell. The two main types of receptors that these ligands can attach to are soluble cytoplasmic proteins or transmembrane receptors. An example of a cytoplasmic protein is a steroid receptor, where the ligand must be hydrophobic to get through the cell membrane, then attach to their desired protein within the cytoplasm.

Receptor/Ligand binding affinity

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The interaction of most ligands with their binding sites can be characterized in terms of a binding affinity. In general, high affinity ligand binding results from greater intermolecular force between the ligand and its receptor while low affinity ligand binding involves less intermolecular force between the ligand and its receptor. In general, high affinity binding involves a longer residence time for the ligand at its receptor binding site than is the case for low affinity binding. High affinity binding of ligands to receptors is often physiologically important when some of the binding energy can be used to cause a conformational change in the receptor, resulting in altered behavior of an associated ion channel or enzyme.

A ligand that can bind to a receptor, alter the function of the receptor and trigger a physiological response is called an agonist for that receptor. Agonist binding to a receptor can be characterized both in terms of how much physiological response can be triggered and the concentration of the agonist that is required to produce the physiological response. High affinity ligand binding implies that a relatively low concentration of a ligand is adequate to maximally occupy a ligand binding site and trigger a physiological response. Low affinity binding implies that a relatively high concentration of a ligand is required before the binding site is maximally occupied and the maximum physiological response to the ligand is achieved. In the example shown to the right, two different ligands bind to the same receptor binding site. Only one of the agonists shown can maximally stimulate the receptor and it can be defined as a "full agonist". An agonist that can only partially activate the physiological response is called a "partial agonist". Ligands that bind to a receptor but fail to activate the physiological response are receptor "antagonists". In this example, the concentration at which the full agonist (red curve) can half-maximally activate the receptor is about 5 x 10^-9 Molar (nM = nanomolar). In the example shown to the left, ligand binding curves are shown for two ligands with different binding affinities. Ligand binding is often characterized in terms of the concentration of ligand at which half of the receptor binding sites are occupied (k_d). The ligand illustrated by the red curve has a higher binding affinity and smaller k_d than the ligand illustrated by the green curve. If these two ligands were present at the same time, more of the higher affinity ligand would be bound to the available receptor binding sites. This is how carbon monoxide can compete for oxygen in binding to hemoglobin, resulting in carbon monoxide poisoning.

See also

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• Allosteric regulation

References

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• Ligand binding to hormone receptors in Endocrinology: An Integrated Approach by Stephen Nussey and Saffron Whitehead (2001) Published by BIOS Scientific Publishers Ltd. ISBN 1859962521.
• Molecular Recognition Processes in Molecular Biology of the Cell 3rd edition (1994) by Bruce Alberts, Dennis Bray, Julian Lewis, Martin Raff, Keith Roberts and James D. Watson. See Figure 3-9, Equilibrium ligand binding.

Biochemistry