Cysteine proteases
| Cysteine proteases | ||
|---|---|---|
| Enzyme classification | ||
| EC, category | 3.4.22.- | |
| Response type | Proteolysis | |
The cysteine proteases are a group of enzymes that belong to the hydrolases and their subgroup of the proteases or peptidases .
The cysteine proteases (thiol proteases) include, for example, the enzyme papain , as well as the caspases . They are characterized by a so-called catalytic diad, consisting of the amino acids cysteine and histidine . This arrangement forms the active center of the enzyme.
The peptidase database MEROPS counts nine clans of cysteine proteases with almost 60 families .
Reaction mechanism of the cysteine proteases
Essentially, the proteases break the peptide bond .
This happens as follows: The cysteine is activated by the histidine through base catalysis , i. That is , the proton of the thiol group is transferred to the nitrogen of the histidine (top left in the picture). The now positively charged histidine is stabilized by the negatively charged aspartate side chain (not shown). A nucleophilic attack of the thiolate on the C1 atom of the peptide bond takes place (top right), so that a tetrahedral transition state arises (center right). The nitrogen of the peptide bond is now acid-catalyzed , i. that is, it is split off protonated by the histidine. There is now a thioester bond between the enzyme and the rest of the peptide chain, a so-called acyl enzyme (bottom right). This intermediate is then nucleophilically attacked by water on the partially positively charged C1 atom (bottom left). A tetrahedral transition state forms again before the remaining peptide with a new carboxy group is split off and the remaining proton is protonated from the water, the now free cysteine side chain again, to the thiol (center left). There are now two partial peptides with a new amino terminus and a new carboxyl terminus.