Biochemistry and Molecular Biology - Belyasova N.A. 2002

Structure and Functions of Cellular Components
Proteins. Organizational Features and Functions of Enzymes
Structural Features of Enzyme Molecules

Enzymes are specialized, highly efficient catalysts for Chemical Reactions. The vast majority of cellular reactions take place with the participation of enzymes, and a single Cell may contain up to 1,000 different enzymes. Currently, the Functions of more than 2,000 enzymes are known, several hundred of which have been studied in greatest detail, with their Amino acid sequences and spatial structures fully determined.

Enzymatic Catalysis accelerates chemical reactions by a factor of 10⁶—10¹⁶! When isolated from The Cell without disrupting their native Structure, enzymes retain their activity, making it possible to use them in cell-free reactions.

Enzyme molecules vary in molecular weight—ranging from 10,000 to 1,000,000 daltons (Da) and higher; however, the majority of enzymes are Globular Proteins with molecular weights in the hundreds of thousands of daltons, composed of subunits (protomers). The packing of subunits within a multimeric (multi-subunit) protein occurs through the same types of interactions involved in The formation of the protein's tertiary structure. Dimers and tetramers predominate among multimeric enzymes, whereas hexamers and octamers are less common, and trimers and pentamers are extremely rare.

Multimeric enzyme proteins may contain several types of protomers that differ in certain aspects of their primary and tertiary structures. Certain chemical and Physical Properties of a multimeric enzyme depend on The ratio of these Different types of protomers, and such variant forms of a multimeric enzyme are termed Isoenzymes (isozymes). For example, Lactate dehydrogenase, which catalyzes the reversible oxidation of lactic acid in Muscles, consists of four subunits of two types (H and M) and exists in five isoenzymes (HHHH, HHHM, HHMM, HMMM, MMMM). These isoenzymes differ from one another in activity, molecular weight, electrophoretic mobility, Tissue and organ localization, and sensitivity to regulatory molecules. The existence of isoenzymes enables the Organism to alter their relative proportions and thereby regulate metabolic activity.

The Study of enzyme molecular structure has revealed several General Principles in their Organization. The polypeptide chain that forms the protein globule is folded in a rather complex manner. Some regions of this chain form a-helices or ß-structures, while others adopt irregular yet well-defined Conformations. Closely apposed and alternating, these structures pack into functionally active domains. The surface of the protein globule is predominantly populated by polar groups and charged atoms, with ionic bonds (salt bridges) sometimes forming between oppositely charged groups (e.g., between the side chains of Glu^- and Lys⁺). The interior of the protein globule constitutes a nonpolar environment; the Hydrophobic core is formed by nonpolar groups belonging mainly to the aliphatic and aromatic side chains of Alanine, valine, isoleucine, leucine, Methionine, phenylalanine, and Tryptophan. Functionally important polar amino acid residues are also oriented toward the interior of the globule, where they associate with one another.

A critical component of the enzyme molecule is the Active Site, which typically takes the form of a cleft or depression within the enzyme globule. The binding of the substrate and its conversion into product occur at the active site. The active site is almost invariably formed by a small number of amino acid residues that are generally far apart from each other in the primary polypeptide chain. Functionally, the active site can be divided into two regions: the binding site and the catalytic site.

The amino acid residues that constitute the binding site ensure the retention of the substrate within the active site. It is the "architecture" of the binding site that determines the complementarity of the enzyme to the substrate structure, thereby dictating substrate Specificity. Substrate attachment frequently occurs via interaction with the ε-amino group of a Lysine side chain located in the substrate-binding region. The carboxyl group of glutamic acid or the sulfhydryl group of Cysteine can serve the same function. More often, however, the Formation of the enzyme-substrate complex proceeds without the formation of covalent bonds, relying instead on weaker forces such as Hydrogen Bonds, Electrostatic Interactions, hydrophobic forces, and Van der Waals interactions.

The catalytic site of the enzyme comprises amino acid residues that participate directly in catalysis. Known as catalytic groups, they are most commonly represented by residues of Serine, Histidine, tryptophan, Arginine, cysteine, aspartic acid, glutamic acid, and Tyrosine. The final assembly of the catalytic site in many enzymes may occur at the moment of substrate binding.

In addition to the active site, most enzymes possess an allosteric site. This region of the molecule is designed for binding regulatory effectors, which alters the Tertiary Structure of the protein. This conformational shift also affects the geometry of the active site, leading to an increase or decrease in the catalytic activity of the enzyme. This phenomenon forms The basis of allosteric Introduction/15.html">Regulation of enzyme Activity.

Some enzymes exhibit polyfunctionality—The ability to catalyze multiple enzymatic reactions. This phenomenon is explained by the fact that during the formation of the tertiary structure, The polypeptide chains of such enzymes fold into several functionally and sterically distinct globular regions, or domains, each characterized by its own distinct catalytic activity.