Cysteine protease

The cysteine ​​proteases are a group of enzymes, which are among the hydrolases and their sub- group of proteases or peptidases.

The cysteine ​​( thiol protease ) include, for example, the enzyme papain, as well as the caspases. They are characterized by a so-called catalytic diad composed of the amino acids, cysteine ​​and histidine. This arrangement forms the active site of the enzyme.

The peptidase database MEROPS counts nine clans of cysteine ​​proteases, with about 60 families.

Reaction mechanism of cysteine ​​proteases

Substantially the proteases cleave the peptide bond.

This is done as follows: The base catalysis cysteine ​​is activated by the histidine, that is, the proton of the thiol group is transferred to the nitrogen of histidine (top left). The now positively charged histidine (not shown ) through the negatively charged aspartate side chain stabilizes. It carries out a nucleophilic attack of the thiolate to the C1 atom of the peptide bond (top right), so that a tetrahedral transition state is formed ( center right ). The nitrogen of the peptide bond is now under acid catalysis, that is, it is protonated by the histidine cleaved. It is now a thioester bond between the enzyme and the rest of the peptide chain before, a so-called acyl-enzyme ( bottom right). This intermediate is then attacked by nucleophilic water at the partially positively charged C1 atom ( bottom left). It is again a tetrahedral transition state before the remaining peptide carboxy group is cleaved with new and the remaining proton from the water, which now again free cysteine ​​thiol to the protonated ( center left ). There are thus now in front of two partial peptides with a new amino terminus or the carboxyl terminus of a new.

Examples

• Caspases
• Bromelain
• Papain

Other types of protease

• Serine proteases
• Aspartic proteases
• Metalloproteases