Cysteine in Nucleophilic Attack

Cysteine proteases are a class of enzymes that have been widely studied over the years. The overall principles of substrate recognition, catalysis, and inhibition are now reasonably well documented. This enzyme class includes the plant proteases such as papain, actinidin, and bromelain, and several mammalian lysosomal cathe-psins. By far the majority of the literature reports dealing with cysteine proteases describe results obtained with the enzyme papain, because it is considered to be the archetype of this enzyme class. 

Probably the aspect of primary importance for the catalytic activity of cysteine proteases is the high nucleophilicity of the active-site thiol group. It is now generally accepted that the active form of papain and of cysteine proteases in general consists of a thiolate-imidazolium ion-pair, built from Cys25 and Hisl59. 

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