Key Concepts of Section 3.3

• A protein’s function depends on its ability to bind other molecules, known as ligands. For example, antibodies bind to a group of ligands known as antigens, and enzymes bind to reactants called substrates that will be converted by chemical reactions into products.

• The specificity of a protein for a particular ligand refers to the preferential binding of one or a few closely related ligands. The affinity of a protein for a particular ligand refers to the strength of binding, usually expressed as the dissociation constant K_d.

• Proteins are able to bind to ligands because of molecular complementarity between the ligand-binding sites and the corresponding ligands.

• Enzymes are catalytic proteins that accelerate the rates of cellular reactions by lowering the activation energy and stabilizing transition-state intermediates (see Figure 3-22).

• An enzyme’s active site, which is usually only a small part of the protein, comprises two functional parts: a substrate-binding site and a catalytic site. The substrate-binding site is responsible for the exquisite specificity of enzymes owing to its molecular complementarity with the substrate.

• The initial binding of a substrate (S) to an enzyme (E) results in the formation of an enzyme-substrate complex (ES), which then undergoes one or more reactions catalyzed by the catalytic groups in the catalytic site until the final product (P) is formed.

• From plots of reaction rate versus substrate concentration, two characteristic parameters of an enzyme can be determined: the Michaelis constant, K_m, a rough measure of the enzyme’s affinity for converting substrate into product, and the maximal velocity, V_max, a measure of its catalytic power (see Figure 3-24).

• The rates of enzyme-catalyzed reactions vary enormously, with turnover numbers (numbers of substrate molecules converted to product at a single active site at substrate saturation) ranging from fewer than 1 to 6 × 10⁵ molecules per second.

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• Many enzymes catalyze the conversion of substrates to products by dividing the process into multiple discrete chemical reactions that involve multiple distinct enzyme-substrate complexes (ES′, ES″ etc.).

• Serine proteases hydrolyze peptide bonds in substrate proteins using as catalytic groups the side chains of Ser-195, His-57, and Asp-102. Amino acids lining the side-chain-specificity binding pocket in the binding site of serine proteases determine the residue in a substrate protein whose peptide bond will be hydrolyzed and account for differences in protease specificity (for example, trypsin vs. chymotrypsin and elastase).

• Enzymes often use acid-base catalysis mediated by one or more amino acid side chains, such as the imidazole group of His-57 in serine proteases, to catalyze reactions. The pH dependence of protonation of catalytic groups (pK_a) is often reflected in the pH-rate profile of the enzyme’s activity.

• Nonpolypeptide small molecules or ions, called cofactors or prosthetic groups, bind to the active sites of some enzymes and play an essential role in enzymatic catalysis. Small organic prosthetic groups in enzymes are also called coenzymes; many vitamins, which cannot be synthesized in higher animal cells, function as or are used to generate coenzymes.

• Enzymes in a common metabolic pathway are often located within the same cellular compartments and may be further associated as domains of a monomeric protein, subunits of a multimeric protein, or components of a protein complex assembled on a common scaffold (see Figure 3-30).