Intermolecular forces enzyme-substrate binding

A substrate binds an enzyme at the active site. Substrate-enzyme binding is based on weak intermolecular attractions contact forces, dipole forces, and hydrogen bonding. Steric effects also play an important role because the substrate must physically fit into the active site. Some enzymes have confined active sites, while others are open and accessible. A restricted active site can lead to high selectivity for a specific substrate. Low specificity can be advantageous for some enzymes, particularly metabolic and digestive enzymes that need to process a broad range of compounds with a variety of structures. Because enzymes are composed of chiral amino acids, enzymes interact differently with stereoisomers, whether diastereomers or enantiomers. 

Reversible inhibitors bind an enzyme through weak, intermolecular forces and establish an equilibrium of being bound or unbound to the enzyme. A competitive inhibitor binds at the active site and prevents the substrate from binding. A noncompetitive inhibitor binds an allosteric site on the enzyme and prevents conversion of the substrate to product. Uncompetitive inhibitors bind the enzyme-substrate complex and make it inactive. All three types of inhibitors show characteristic, distinctive features in a Lineweaver-Burk plot. 

Like an enzyme, an asymmetric catalyst binds its substrate, performs a reaction, and releases the product three steps. Chiral auxiliaries have three analogous steps attach, react, and cleave. The advantage of an asymmetric catalyst over an auxiliary is that binding to the substrate is reversible and involves weak, intermolecular forces instead of covalent bonds. Binding and release of the substrate occur in the same reaction vessel as the stereocenter-forming reaction. 

FIGURE 18.18 The binding of a substrate to an enzyme and the subsequent reaction of the substrate. As this schematic figure suggests, the size and shape of the active site play a role in determining which substrates bind. Equally important are the strengths of the intermolecular forces between nearby groups on the enzyme and substrate. 

Geometrical distortion of the substrate by the enzyme is unlikely to be a significant factor in catalysis. The intermolecular forces of binding are generally too weak and flexible to distort the substrate. The intermolecular force field cannot overcome the intramolecular force field of the substrate. 

All enzymes are proteins, which are linear sequences of amino acids linked by peptide bonds. The folding of these sequences determined the secondary structure (such as a-helix, p-sheet or p-turn) and tertiary structure. Therefore, the properties of an en me are actually presumed from its sequence of amino acids. Some amino acids, dubbed hot spots , especially the ones in the active site where substrate binds, are sensitive to catalytic properties of an enzyme. Substitution of these important amino acids can significantly improve the activity or enantioselectivity toward a certain reaction. Protein stability is also maintained by the intramolecular and intermolecular interactions between residues of amino acids, including van der Waals forces, hydrophobic forces, electrostatic forces, hydrogen bonds and disulfide bonds. Detailed analysis of these amino acids, usually located in the protein surface, sheds light on the protein design for better thermostability. 

The combination of the enzyme and the substrate is called the mzyme-siibstrate complex. Although Figure 1424 shows both the active site and its complementary substrate as having rigid shapes, there is often a fair amount of flexibility in the active site. Thus, the active site may change shape as it binds the substrate. The binding between the substrate and the active site involves intermolecular forces such as dipole-dipole attractions, hydrogen bonds, and London dispersion forces. 

An enzyme (denoted here by E) is generally a protein which contains one or more active sites to which a reactant molecule can bind. In a sense, enzymatic catalysis is intermediate between homogeneous and heterogeneous catalysis in that the active site or sites are on the surface of the enzyme but the enzyme and reactant molecules are in the same solution phase. In the first step of the catalysed reaction, the reactant molecule, usually referred to as the substrate (S), binds to an active site on the enz5mie, in a process which is reversible and which generally utilises intermolecular forces, of the kind considered in Sect. 1.4, to form an enzyme-substrate complex (ES). As in other kinds of catalysis, the role of the enzyme is to... 

M FIGURE 13.21 En e-Substrate Binding A substrate (or reactant) fits into the active site of an enzyme much as a key fits into a lock. It is held in place by intermolecular forces and forms an enzyme-substrate complex. (Sometimes temporary covalent bonding may also be involved.) After the reaction occurs, the products are released from the active site. 

The specificity of an enzyme for its substrate results from the particular amino acid side chains that reside at the active site (Section 22.1). The side chains bind the substrate to the active site using hydrogen bonds, van der Waals forces, and dipole-dipole interactions— the same intermolecular interactions that hold molecules together (Section 3.9). A more in-depth discussion of the interaction between the enzyme and the substrate can be found in Section 23.8. 

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