Читать книгу Enzyme-Based Organic Synthesis - Cheanyeh Cheng - Страница 15

The science by which molecules interact via geometric orientations of atoms is called molecular recognition. The specific geometry of a molecule controls how it will react with other substances. Nearly, all enzymes are made up of more than 100 amino acid residues. However, an enzyme binds a substrate molecule at the catalytic active site that is just a small pocket or cleft region of the enzyme. The 3D structure of the active site is surrounded by amino acid side chains that come from different parts of the linear amino acid sequence. Water is usually excluded unless it is a reactant. The nonpolar character of much of the cleft enhances the binding of substrate. However, the cleft may also contain some polar residues that create a microenvironment essential for catalysis and extraordinary enzyme specificity. The specificity of binding of atoms in a substrate to the active site leads the proposed lock‐and‐key model of interaction between the substrate and enzyme by Emil Fischer in 1894 that points out the binding of a substrate to an enzyme just like the relationship of a key to a lock. The lock‐and‐key model is now modified to the induced fit model by Daniel Koshland in 1958 with the evident that the enzyme and substrate must adjust to fit one another to take up a configuration to stabilize the transition state [10, 11].

However, to assure the necessary geometric accuracy of the substrate binding and the orientation of catalytic functional group for enzyme interaction, the number of specific binding sites or points needed between the substrate and the active site of enzyme depends on the size of a molecule. For a large molecule such as glycyl tyrosine, a dipeptide, can bind carboxypeptidase A through total of five points at the active site [10, 12]: the electrostatic force, two hydrogen bonds, the hydrophobic interaction, and the coordination bonding to perform the hydrolysis of peptide bond of glycyl tyrosine. For small molecule such as carbon dioxide and water can coordinative bind carbonic anhydrase with only one point through the cofactor zinc ion and react to form bicarbonate or the reversible reaction [10]. Another example for small molecule is the binding of a covalent adduct formed between pyruvate and nicotinamide adenine dinucleotide (NAD⁺) to lactate dehydrogenase (LDH) to produce lactate in which only two binding points, namely, the carbonyl group and the carboxylate group, of pyruvate are used to bind with the LDH [12]. The number of binding sites of an enzyme to the substrate is important in determining the type of enzyme specificity. The molecular recognition for enzyme specificity has been categorized into three major types of specificities: substrate specificity, regiospecificity, and stereospecificity [13].