DIFFERENCE BETWEEN RECEPTORS AND ENZYMES

What is the difference and similarities between receptors and enzymes?

Like enzymes, receptors are common targets in drug discovery. Receptors act as switches that can be turned on or off. When turned on, receptors initiate a cascade of events that ultimately produce a biological response.

The body contains thousands of different receptors. Despite their diversity, almost all receptors can be classified into a handful of different receptor superfamilies.

Receptors bind molecules that either activate or suppress the normal function of the receptor. The impact of receptor binding can be modeled mathematically to allow better understanding of receptor function. Better understanding of receptor function ultimately allows for the design of safer, more effective drugs.

Both enzymes and receptors are proteins, and therefore both biological structures share many fundamental similarities. Regardless their roles within a biological system are distinct from one another.

Similarities
As proteins, both enzymes and receptors possess the same aspects of primary, secondary, tertiary, and quaternary structure. Just as with enzymes, proper folding of a receptor depends on environmental factors, including temperature and pH. The shape of a receptor is crucial because, like enzymes, receptors operate by binding other molecules, called ligands.

The similarities between enzymes and receptors allow both systems to be modeled with many of the same mathematical equations. Most treatments of receptors and enzymes appear to be very different, but the derivations and theories can largely be recycled between the two.

Difference
The primary difference between receptors and enzymes lies in what they do. Enzymes convert a substrate to a product. Receptors do not catalyze a reaction or otherwise convert a ligand. Instead, receptors bind a ligand, or primary messenger.

Upon binding a ligand, a receptor changes its conformation to initiate a series of events. These events may involve a number of other agents, including enzymes (effectors), binding proteins (transducers), and/or other signaling molecules (secondary messengers).

The number of other players in the pathway depends on the particular receptor. Each ligand can potentially produce many secondary messengers, a phenomenon known as signal amplification. Ultimately, the entire process generates an observable biological response.

X-RAY CRYSTALLOGRAPHY BASIC INFORMATION AND TUTORIALS

What is X-Ray Crystallography?

X-ray crystallography is the most important method for determining protein structure. X-ray crystallography is a technique by which an x-ray beam is scattered upon contact with a crystallized protein. The pattern of scattering can be used to determine the relative position of the atoms in the crystal.

The quality of an x-ray crystal structure is described in terms of its resolution. Resolution is listed in units of angstroms (Å). A high resolution for an x-ray structure might be 0.5–2.0 Å with a lower number indicating better resolution.

Once the data has been processed, the positions of nonhydrogen atoms appear as spheres in three-dimensional space in an image called an electron density map. The electron density map shows atoms as spheres.

Figure 9.1 shows the impact of resolution on the readability of an electron density map. Image (a) has a resolution of 0.62 Å. Atoms are nearly distinct and separate from other atoms. Image (b) has a resolution of 1.2 Å. Atoms are still clear but somewhat larger.

As the resolution drops to 2.0 Å (c), the spheres of the individual nuclei become unclear. The feature that now dominates the electron density map is the peptide backbone. Once the resolution drops to 3.0 Å (d) and 4.0 Å (e), single atom branches off the backbone are nearly imperceptible. At 5.0 Å (f), folds of the backbone can mistakenly appear to merge together.

Solving an x-ray structure requires correctly assigning atoms in the protein to match the electron density map. Before solving a structure, an x-ray crystallographer already has the sequence of the target protein from the molecular biology team.

The x-ray crystallographer begins to solve the structure by aligning the most obvious residues, such as the aromatic rings, into the electron density map. Less obvious residues then fall into place as possibilities become more limited. If an electron density map has a low resolution (6–8 Å), then only general features such as a-helices or b-sheets may be clear. The confident placement of individual residues is not possible.

A protein will generally have one or more random coil regions in its overall structure. Random coils, as the name suggests, do not have a regular, folded structure and undergo rapid, continuous conformational changes. These regions appear indistinct even in an otherwise high resolution x-ray structure. Fortunately, binding and active sites generally occupy ordered protein regions that are amenable to characterization by x-ray crystallography.

Knowing the structure and shape of the binding site of a target allows the discovery team to make informed decisions about molecules that will bind to the target. Is the binding site deep or shallow? Are the amino acid residues in the binding site polar, nonpolar, or charged?

The properties of the binding site determine the optimal, complementary properties needed in a drug that will interact with the binding site. Often molecules can be cocrystallized with an enzyme target. The x-ray structure of the complex shows both how a compound fills the binding pocket and precisely where a compound may be modified to better fill the active site.