Structural Biochemistry/Enzyme/Catalytic Triad and S1 Pocket
Catalytic Triad[edit | edit source]
A catalytic triad is a group of three amino acids that are found in the active sites of some proteases involved in catalysis. Three different proteases that have catalytic triads are: chymotrypsin, trypsin and Elastase. In chymotrypsin, the catalytic triad is made from serine 195, histidine 57, and aspartate 102. The side chain of serine is bonded to the imidazole ring of the histidine residue which accepts a proton from serine to form a strong alkoxide nucleophile in the presence of a substrate for attack. The aspartate residue orients histidine to make it a better proton acceptor via hydrogen bonding and electrostatic reactions. The combined cooperation results not only in better orientation and stabilization, but also in a sufficient nucleophile that is capable of attack.
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Catalytic Dyad[edit | edit source]
In contrast to the catalytic triad described above, the catalytic dyad comprises only two amino acid residues, usually one acting as nucleophile and the other one representing a proton donor to stabilize the product(s). A well known example is the HIV-1 Protease, in which the active site is formed by two aspartic acid residues (Asp25 and Asp25'), one residing in its deprotonated carboxylate form while the other one is protonated to the corresponding carboxylic acid.
S1 Pocket[edit | edit source]
The S1 pocket helps to explain why chymotrypsin, trypsin, and elastase cleave certain peptide binds. The S1 pocket is a deep hydrophobic pocket that allows long, uncharged amino acids like phenylalanine and tryptophan to fit in chymotrypsin. Binding in the S1 pocket positions the adjacent peptide bond at the active site for cleavage. Trypsin cleaves peptide bonds after arginine and lysine which are amino acids with long and positively charged side chains because its S1 pocket contains an aspartate that is negatively charged which attracts and stabilizes the positively charged side chains of arginine and lysine in the substrate. Elastase cleaves peptide bonds after amino acids like alanine and serine which have small side chains because its S1 pocket has two bulky valine residues that decreases the size of the pocket opening so only small chains can enter.
In the figure to the right, it shows that some proteases can have more complex specificity patterns. there are more pockets on their surface to recognize other groups on the substrate. the substrate with the enzyme is the P group that is colored in red and these bind to enzymes labeled in blue. The sessile bond is the red bond between the carbon and nitrogen is also known as the reference point.