Structural Biochemistry/Catalytic Strategies/Covalent Catalysis
[[:Image:]][[:Image:]]== Covalent Catalysis: A Definition ==
Covalent Catalysis is one of the four strategies that an enzyme will employ to catalyze a specific reaction. In this reaction the enzyme contains a reactive group, usually a nucleophilic residue which reacts with the substrate through a nucleophilic attack. This is usually carried out by pyridine, which is a better nucleophile than water that has a pKa of 5.5. The charge loss in the reaction during transitional state will then cause hydrolysis to accelerate. The residue becomes covalently attached to the substrate throughout the catalytic reaction adding an additional intermediate which helps stabilize later transition states by lowering the activation energy. The covalent bond is then broken to regenerate enzymes.
Examples of Enzymes that Participate in Covalent Catalysis
Examples of enzymes that participate in covalent catalysis include the proteolytic enzyme chymotrypsin and trypsin in which the nucleophlie is the hydroxyl group on the serine. Chymotrypsin is a degradative protease of the digestive system. It catalyzes the cleavage of peptide bonds that are adjacent to large aromatic or nonpolar residues. It cleaves the peptide bond on the carboxyl terminus side of the protein. The chymotrypsin has three main catalytic residues termed as the catalytic triad. These are His 57, Asp 102 and Ser 195. Upon deprotonation the serine residue becomes a powerful nucleophile due to its alkoxide that will attack the relatively unreactive carbon of the carbonyl in the protein. The figure shows the catalytic triads in neutral and deprotonated form. Courtesy of Kiongho; www.nsm.buffalo.edu/~kiongho/
Typical residues used in covalent catalysis are Lys, His, Cys, Asp, Glu, and Ser and some other coenzymes.
An example of covalent catalysis is shown below: