Biochemistry and Molecular Biology - Belyasova N.A. 2002

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

Enzymes are highly specific and efficient catalysts of 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, of which several hundred have been studied in the 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 damaging their native Structure, enzymes retain their activity, making it possible to use them in cell-free reactions.

Enzyme molecules vary widely in molecular mass—from 10,000 to 1,000,000 daltons (Da) and higher; however, most enzymes are Globular Proteins with a molecular mass of several hundred thousand daltons, built from subunits (protomers). The packaging of subunits into a multimeric protein (consisting of multiple subunits) is achieved through the same types of interactions involved in The formation of a protein's tertiary structure. Dimers and tetramers predominate among multimeric enzymes, whereas hexamers and octamers are less common, and trimers and pentamers occur very rarely.

Multimeric enzyme proteins may contain several types of protomers that differ in certain features of their primary and tertiary structures. Some of the chemical and Physical Properties of a multimer depend on The ratio of these Different types of protomers, and such variant forms of a multimeric enzyme are called 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 mass, electrophoretic mobility, localization in Organs and Tissues, and sensitivity to regulatory substances. The existence of isoenzymes enables the Organism to alter their ratio and thereby regulate metabolic activity.

The Study of enzyme molecule structures has revealed several general patterns in their Organization. The polypeptide chain forming 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 strictly defined Conformations. Tightly packed and alternating, these structures fold into functionally active domains. The surface of the protein globule is enriched mainly with polar groups and charged atoms, with ionic bonds (salt bridges) sometimes forming between oppositely charged groups (for example, between the side chains of Glu^- and Lys⁺). The interior of the protein globule represents a non-polar environment; the Hydrophobic core is formed by non-polar groups belonging primarily to the aliphatic and aromatic side chains of Alanine, valine, isoleucine, leucine, Methionine, phenylalanine, and Tryptophan. Functional polar amino acid residues are also oriented toward the interior of the globule, where they associate with one another.

A crucial part of the enzyme molecule is the Active Site, which typically has the shape of a cleft or depression within the enzyme globule. The binding of the substrate and its conversion into a product take place at the active site. The active site is almost invariably formed by a small number of amino acid residues that are generally located quite far apart in the polypeptide chain. Functionally, the active site can be conventionally divided into two regions: the binding site and the catalytic site.

The amino acid residues that form the binding site ensure the retention of the substrate within the active site. It is precisely the "architecture" of the binding site that determines its complementarity to the substrate structure, i.e., the binding Specificity of the enzyme. Substrate attachment often occurs through interaction with the ε-amino group of a Lysine radical located in the substrate-binding region. The carboxyl group of glutamic acid or the sulfhydryl group of Cysteine can serve this same function. However, the Formation of the enzyme-substrate complex more frequently occurs without the creation of covalent bonds, driven instead by weaker forces such as hydrogen and electrostatic bonds, hydrophobic interactions, and Van der Waals forces.

The catalytic site of the enzyme includes 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 formation of the catalytic site in many enzymes may occur at the moment the substrate binds.

In addition to the active site, most enzymes contain an allosteric site. This region of the molecule is designed to bind regulatory substances, resulting in an alteration of the protein's tertiary structure. This distortion also affects the conformation of the active site, leading to an increase or decrease in the enzyme's catalytic activity. This phenomenon underlies the allosteric Introduction/15.html">Regulation of enzyme Activity.

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