Catalytic triad
In biochemistry, a catalytic triad is a special arrangement of three amino acids in the active center of some enzymes. The catalytic triad can be used to catalyze the cleavage of a substrate in hydrolases and the transfer of a part of the substrate to a second substrate in transferases . The three amino acids act as acid, base and nucleophile and enable covalent catalysis .
The amino acid residues of the catalytic triad can be far apart in the amino acid sequence ( primary structure ) and can only be brought into spatial proximity through the enzyme folding, the formation of a complex three-dimensional structure.
construction
Structure in serine proteases
In serine proteases, the catalytic triad is formed from aspartic acid , histidine and serine , the amino acid residues of which are linked by hydrogen bonds . The aspartic acid residue is in a pocket inaccessible to the solvent and forms a hydrogen bond to the NH group of the histidine residue. The histidine polarized in this way, in turn, forms a hydrogen bond with the second ring-bound nitrogen to the OH group of the serine residue. The hydrogen-oxygen bond is thereby strongly polarized and the nucleophilicity of the oxygen is further increased.
Structure in thiol / cysteine proteases
Cysteine proteases (also called thioproteases) have both catalytic di- and triads. The catalytic diad consists of cysteine and histidine , the triad of cysteine-histidine- asparagine / aspartic acid / glutamine or glutamic acid .
Catalysis mechanism
As endopeptidases, serine proteinases catalyze the hydrolytic cleavage of peptide bonds in proteins . After the formation of the enzyme-substrate complex, a nucleophilic attack of the serine-oxygen takes place on the carbonyl carbon of the peptide bond with the formation of a covalent tetrahedral intermediate stage (in the so-called oxyanion gap). The negative charge in the transition state is stabilized by hydrogen bonds . In addition, the hydrogen from the hydrogen bond is transferred to the histidine. In the second step, the hydrogen that has just been transferred is used to protonate the peptide nitrogen, which breaks the peptide bond. The resulting N-terminus of the cleaved protein diffuses away and is replaced by water from the solvent. A hydrogen bond to the histidine residue enables the nucleophilic attack of the water on the serine-bound carbonyl carbon. After the hydrogen has been completely transferred to the histidine, the last step is the formation of the original hydrogen bond between serine and histidine, whereby the covalent bond to the substrate is cleaved and the newly formed C-terminus of the cleaved protein can diffuse away. Due to the covalent intermediate stages, the mechanism belongs to the group of covalent catalysis , while the influence of the aspartate residue on the histidine represents electrostatic catalysis .
literature
- D. Voet, JG Voet: Biochemie , VCH, 1994, ISBN 3-527-29249-7 , p. 368 ff.
Individual evidence
- ↑ Guy Dodson, Alexander Wlodawer: Catalytic triads and their relatives . In: Trends in Biochemical Sciences . tape 23 , no. 9 , September 1, 1998, pp. 347-352 , doi : 10.1016 / S0968-0004 (98) 01254-7 , PMID 9787641 .
- ↑ Andrew R. Buller, Craig A. Townsend: Intrinsic evolutionary constraints on protease structure, enzyme acylation, and the identity of the catalytic triad . In: Proceedings of the National Academy of Sciences . tape 110 , no. 8 , February 19, 2013, p. E653-661 , doi : 10.1073 / pnas.1221050110 , PMID 23382230 , PMC 3581919 (free full text).