Enzyme Mechanism – Key and Lock
How does an enzyme function? Let’s discuss some aspects of the Enzyme Mechanism, shape, hydrogen bonds, and Selectivity. The mechanism explains how enzymes function with specific substrates. Induced fit requires substrates that are capable of changing shape. Without these, enzymes cannot induce fit.
Similarly, enzymes that do not have the proper shape cannot induce fit. But the key here is the Selectivity. Here are some examples of enzymes with Selectivity.
The lock and key model proposes that the substrate and enzyme have complementary geometric shapes. In other words, the correct shape of the enzyme fits in the substrate and vice versa. As a result, the substrate and enzyme are very specific, and the correct substrate fits the enzyme’s active site exactly. The key and lock model is a simplified version of this theory, also referred to as the “induced fit” model.
The induced-fit model suggests that the catalytic group of an enzyme is not rigid or static, whereas the lock and key model requires the active site to be flexible. The induced-fit model also requires a transition state between the substrate and enzyme before the corresponding changes in the substrate are made. The active site of an enzyme is optimized to bind a substrate transition state, and the process is accelerated. Therefore, the key and lock model offers a better explanation of the mechanism of binding.
The lock and key hypothesis, developed by Emil Fischer in 1894, explains how an enzyme can affect the properties of molecules in solution. In this hypothesis, the enzymes react with only a few similar compounds, while others interact with many compounds. It is a well-known fact that enzymes are highly specific to their substrates. This mechanism of enzyme activity also provides a way to explain why some substrates don’t cause a chemical reaction.
The structure of the active site of an enzyme resembles a lock and key. To work, the enzyme must bind to a specific substrate. The lock and key model assumes that the substrate and enzyme share a common shape. The enzyme will fail to function if they don’t share the same shape. The induced-fit model explains how enzymes work by describing how they interact with specific substrates.
An enzyme is a protein that functions as a biological catalyst, speeding up a chemical reaction. Enzymes fold into complex shapes to accommodate smaller molecules. This shape matches the substrate molecules that the enzyme is interacting with. This specificity makes enzymes highly specific. An enzyme illustrated below is called a catalase, and its primary function is to break down hydrogen peroxide into water and oxygen. The corresponding shapes of the active site and substrate are very similar.
The shape of an enzyme’s key and lock is crucial to the mechanism of its action. According to the induced-fit theory, the enzyme’s active site must change shape to match the substrate. When the active site and substrate are perfectly matched, the enzyme’s conformation changes, resulting in a tight fit. The lock and key mechanism work best with tightly-fitting substrates. But the active site of an enzyme is not a static structure.
Emil Fischer coined the ‘lock and key analogy, and it conceptualized the essence of the interactions between enzymes and their substrates. The ‘key’ can be any amino acid residue or a small molecule ligand or receptor. It must fit into a keyhole. The substrate cannot enter the lock if the key is not positioned correctly. Hence, the hydrogen bonds of an enzyme are essential for the interaction of the enzyme with its substrate.
This model describes the hydrogen bonds between the substrate and enzyme in an inverted fashion. The substrate and enzyme molecules have complementary structures and bonding groups. When they are bonded together in an enzyme-substrate complex, the catalytic reaction occurs. Hydrogen bonds are the smallest among these two structural components and allow them to bind to the substrate. This concept also makes enzymes extremely flexible in their function.
Previously, the ‘Lock and Key’ concept has dominated descriptions of protein-ligand interactions. More recently, the ‘combination lock’ approach has improved molecular docking by identifying key elements of these interactions. Hydrogen bonds are particularly important because they can serve as a mechanism that enables binding a protein to a ligand. The key is to understand how hydrogen bonds work in an enzyme-ligand system so that one can design drugs to target specific diseases.
The lock-and-key model describes how an enzyme functions when bound to a specific substrate. In this model, the correct substrate has the appropriate shape and size to fit into the enzyme’s active site. In contrast, an incorrect substrate has the wrong shape or size, which will prevent the enzyme from initiating the reaction and releasing a product. The lock and key model has some limitations, including assuming that enzymes are rigid.
The keyhole-lock-key model incorporates the passage of ligands into and out of tunnels within the enzyme to better understand the mechanisms governing the mechanism of enzymes and enzyme-substrate interactions. A simplified version of this cycle is shown in Fig. 2. The keyholes open a tunnel where the ligand can enter the enzyme’s active site, followed by the reorganization of waters and binding to catalytic residues. The process of binding depends on different aspects of water dynamics and biocatalysis.
Enzymes react with a few kinds of molecules, called substrates. The enzyme’s active site is unique in its geometric shape and can fit only a few of these compounds. The lock and key mechanism explain why only a few types of compounds can be reacted with an enzyme. The substrate can be regenerated and used again for a subsequent reaction by matching the substrate with the enzyme.
Induced fit model
The induced-fit model of enzyme-substrate interactions describes the way substrates bind to the active site of an enzyme. This model suggests that the shape of the substrate is highly compatible with the enzyme’s active site, but the two substances do not have to be an exact fit to achieve binding. In contrast, the lock and key model implies that the shape of the substrate and the active site is complementary.
The induced-fit model of enzyme key and lock posits that the shape of an enzyme depends on the substrate. This model predicts that the substrate will bind to an enzyme whose shape is distorted by the presence of small molecules. This model also assumes that a protein molecule is flexible and that an enzyme will change its shape when it binds to a substrate. This flexibility of the protein molecule makes the induced fit model a good candidate for explaining how enzymes interact with molecules.
In the lock and key model, the substrate and the enzyme share complementary geometric shapes, with the substrate’s shape fitting the keyhole. This theory explains the high specificity of enzymes but does not explain how an enzyme can stabilize a transition state. The induced-fit model explains the stability of the transition state, which is the result of an optimally-matched substrate. However, the induced fit model is more accurate than the lock and key theory despite its simplicity.
The basic concept behind the lock-and-key theory of enzyme action is that the substrate and enzyme have complementary geometric shapes. Both are required to carry out the same chemical reaction and are highly specific. Enzymes can only operate when they bind to the right substrate. This mechanism can be seen in enzyme action and induced-fit theory. But, the key to unlocking a lock is in the substrate. This model does not explain all of the details of enzyme action.
The ‘Combination Lock’ hypothesis is based on a similar principle, where the protein and the ligand have the same set of features. The two molecules can find the perfect fit using the best complementing features. Then, they can interact with each other. This process is referred to as docking. But, before determining which substrate can bind to a protein, a biochemical analysis is required.
The enzyme-substrate interaction can be described in two models: the induced fit model, which describes the binding process when the active site of an enzyme and substrate are not perfectly matched. In this model, the enzyme induces a conformational change within the substrate, causing it to interact with it. The lock-and-key model describes the binding of a perfectly matched substrate and enzyme but is more specific. A lock-and-key model has a static active site and a dynamic, active site, while the induced fit model considers a static enzyme and substrate.
The enzyme-substrate system exhibits conformational flexibility. Daniel Koshland proposed the “induced fit” model that viewed enzyme-substrate interactions as pin tumblers. The pins are shaped like keys and move relative to the lock’s pins. The induced-fit model compares the shear line of cylindrical grooves with the conformational flexibility of enzymes. This model is consistent with various enzyme-substrate systems, from bacteria to bacterial cells.
The application of the induced-fit theory relies on the concept of substrate selectivity. Each enzyme responds to one or two specific substrates. These substrates have a similar molecular structure to the enzyme receptor site. Once the substrate enters the enzyme, it transforms to form a union. However, some substrates are not compatible with the enzyme and fail to induce the desired chemical reaction.
Using this hypothesis, the cylinder is inserted into the binding pocket of an enzyme and moves until it finds the right fit. The induced fit hypothesis is appealing because it explains why certain ligands are not suitable substrates for enzymes. Computational chemists have embraced this theory, and it is the dominant philosophical framework used for molecular docking. These approaches can help predict the behavior of a particular protein-substrate system.