Structural Biochemistry/Protein function/Induced Fit
Induced fit indicates a continuous change in the conformation and shape of an enzyme in response to substrate binding. This makes the enzyme catalytic which results in the lowering of the activation energy barrier causing an increase in the overall rate of the reaction. In other words, when a substrate binds to an enzyme, it will change the conformation of the enzyme. This forms a transitional intermediate which lowers the activation energy and allows the reactants to proceed towards the product at a faster rate. In the case of macromolecules (e.g. proteins), induced fit shows the changes in the shape of a macromolecule in response to a ligand binding so that the binding site of macromolecule conforms more efficiently to the shape of the ligand. The enzyme will change its shape until it is completely complementary to a substrate to activate the enzyme-substrate complex.
As the Enzyme-substrate complex is formed, free energy is released from the formation of the many weak interactions between the enzyme-substrate complex. The free energy that is released is called binding energy and it is maximized only when the "correct" substrate binds to the corresponding specific enzyme. To maximize the release of free energy, the substrate has to be in its transition state. When this happens, the Enzyme-substrate complex becomes a catalyst, which then makes other activation energies lower.
Of enzyme, the active site is the binding site for catalytic and inhibition reaction of enzyme and substrate; structure of active site and its chemical characteristic are of specificity for binding of substrate and enzyme. Two theories for the ways in which enzyme binds to substrate are lock-and-key model and induced fit model; induced fit is the model such that structure of active site of enzyme can be easily changed after binding of enzyme and substrate.
The induced fit model describes the formation of the E-S complex as a result of the interaction between the substrate and a flexible active site. The substrate produces changes in the conformation on the enzyme, aligning properly the groups in the enzyme. It allows better binding and catalytic effects.
This model opposes to the lock and key model that explains the formation of the E-S complex as a result of the binding of complementary geometrical rigid structures, as a lock and a key. The concerted model and the sequential model are models used to explain the allosteric changes of conformation of an enzyme from the T structure to the R structure and vice versa. In the concerted model all the subunits that form the allosteric protein change conformation at once, while in the sequential model the change in conformation of one subunit favors the change in conformation of the other subunits.
The Michaelis Menten model is related to the kinetics of enzyme catalyzed reactions, and describes the relationship between the concentration of substrate and enzyme velocity in a reaction assuming that no allosteric effects exist.
Adenylate kinase is a good example of induced fit. This enzyme functions by slightly changing conformation when both the necessary substrate, ATP and NMP are bound. When both ATP and NMP are bound to this kinase a part of this enzyme called the P-loop moves down and forms a lid over the two groups, this in turns helps to hold the two substrate closer together in order to more easily carry out the reaction of transferring a phosphate group from ATP to NMP. This holds the phosphate group of ATP to a closer proximity to NMP, this also holds the two substrate in the proper orientation. This conformational change helps to carry out the reaction more efficiently by placing the substrate in the right position and closer to each other. We see that this enzyme functions through an induced fit, as the substrate bind the conformation of the enzyme slightly changes in order to better interact with the substrate. When Both substrate are bound various conformational changes occurs, this ensures that the reaction only proceeds when both substrate are present and this eliminates any unnecessary transfer of a phosphate group to water if the NMP is not present.
There are 4 types of catalysis mechanisms that occur after the substrate is bound to an enzyme, causing formation of a transition-state complex and the product:
1. Catalysis by Bond Strain: The new arrangement occurs in the binding of the substrate and the enzyme to ultimate bind together in order to form a strained substrate bond. Such binding will rapid the formation of transition-state. However, the final conformation is not allowed for bulky group and substrate atoms.
2.Catalysis by Proximity and Orientation: Enzyme-substrate interactions shows a clear direction to the reactive groups and make them close to one another. The inducing strains are also reactive which play an important role in the catalysis.
3.Cataylsis Involving Acids and Bases: The strain mechanism makes amino acid act as an acid or base to complete the catalysis reaction. Acid is proton donor, and based is proton acceptor.
4.Covalent Catalysis: Since the substrate is directed to the active site of an enzyme, a covalent bond forms between the substrate and the enzyme. Example: Proteolysis by serine protease is a reaction when proteases have a serine active site that forms a covalent bond between the alkoxyl group of serine and carbonyl carbon of the peptide.
Biochemistry 6th edition. Berg, Jeremy M; Tymoczko, John L; Stryer, Lubert. W.H Freeman and Company. New York