Structural Biochemistry/Enzyme/Substrate specificity
Complex formation and Bond Cleavage
In an enzyme-catalyzed reaction, the substrate must first attaché to the enzyme. The substrate is relatively smaller than the enzyme. Therefore, the substrate is binding with a portion of the enzyme. The substrate is attached to the enzyme with weak bonding forces such as hydrogen bond, electrostatic interactions, and dipole-dipole interactions. The substrates are usually complementary to the enzymes. However, it is possible that they do not fit perfectly each other. These bonding forces help the complex to be more stable. In the case of two substrate reactions involving ternary complex, two substrates must be bound close to each other to precede the reaction. It is impossible to proceed the reaction if two substrates are not adjacent or close each other spatially. From the case, the enzyme should have some steric specificity.
Asymmetric reactions of Symmetric substrates
Symmetric substrates are bound the enzyme asymmetrically in enzyme reactions. For example, when an symmetric substrate binds to an enzyme, the enzyme-substrate complex becomes asymmetric. Further, when two identical substrates binds to the complex, they start to react differently with other molecules.
Achieving Specificity and it's Affect on Catalysis
Specificity is achieved when a substrate binds to an enzyme that has a defined arrangement of atoms in the active site. In order for the substrate to bind correctly the active site must be in a correct shape that matches the enzyme. The substrate binds to the enzyme through multiple weak bonding interactions such as hydrogen bonding, van der Waals forces, and hydrophobic interactions. The lock-and-key model that Emil Fischer devised in 1890 demonstrates the binding between a substrate and the enzyme. This model demonstrates that the enzyme must have a cleft or crevice that corresponds to the shape of the substrate perfectly.
With many years of research it has now been determined that enzymes are more flexible than what scientists once believed and that the lock-and-key model is not an accurate representation. Donald E. Koshland Jr. discovered the induced fit model in 1958 in which the active sites of proteins can change their shape to better fit the substrate. In some cases however, the active site does not modify its shape until the substrate has already been bonded to the enzyme.
This affects the catalysis in many ways. One thing is that when the two bind together they produce something called binding energy which the free energy that two exhibit when they form. Maximum binding energy can only be achieved when the correct substrate binds to the enzyme. This makes substrate specificity very important. It is also at its highest when the substrate is in the transition state. The release of the binding energy when the substrate is in its transition state lowers the activation energy of the reaction and thus making the reaction have a faster rate making the time for product to form much shorter.
John Westley, Enzyme Catalysis
Jeremy M. Berg, Biochemistry