Catalytic triad

As a catalytic triad is called in biochemistry a special arrangement of three amino acids, which features some active sites of enzymes. A catalytic triad found in serine proteases; both catalytic triads and dyads found in thiol and cysteine ​​proteases.

Construction

Structure with serine proteases

In serine proteases, the catalytic triad of aspartate, histidine and serine is formed, the amino acid residues are linked via hydrogen bonds. The aspartate residue is located in an inaccessible for the solvent pocket and forms a hydrogen bond to the NH group of the histidine residue from. The so polarized histidine in turn forms the second ring- bound nitrogen from a hydrogen bond to the OH group of the serine residue. The hydrogen -oxygen bond is strongly polarized and thus the nucleophilicity, of the oxygen is further increased.

Construction at Thiol-/Cysteinproteasen

In cysteine ​​proteases (also called Thioproteasen ) occur in both catalytic di- and triads. The catalytic diad consists of cysteine ​​and histidine, the triad of Cystein-Histidin-Asparagin/Aspartat/Glutamin or glutamic acid.

Catalytic mechanism

Serine endopeptidases catalyze the hydrolytic cleavage of peptide bonds in proteins. After formation of the enzyme-substrate complex is a nucleophilic attack by the serine oxygen to the carbonyl carbon of the peptide bond takes place to form a covalent tetrahedral intermediate. The negative charge is stabilized by hydrogen bonds in the transition state. In addition, the hydrogen from the hydrogen is transferred to histidine. In the second step, the just- transferred to protonation of the hydrogen - nitrogen peptide, whereby the peptide bond is cleaved. The resulting N -terminus of the cleaved protein diffuses away and is replaced with water from the solvent. A hydrogen bond to the histidine residue allows the nucleophilic attack of water at the seringebundenen carbonyl carbon. After complete transfer of the hydrogen to the histidine in the last step is the formation of the original hydrogen bond between serine and histidine which the covalent bond to the substrate is cleaved and the newly emerged C -terminus of the cleaved protein can diffuse away. Because of the covalent intermediate stages of the mechanism part of the group of the covalent catalysis, while the influence of the aspartate residue of the histidine electrostatic catalysis.