Displacement reactions, nucleophilic proteases

The serine proteases catalyze a nucleophilic displacement reaction of a group attached to a carbonyl carbon—such groups comprising esters, thioesters, and amides. The reaction carried out by this class of enzymes is essentially an acyl transfer in which the substrate binds to the enzyme, forming the noncovalent Michaelis complex, followed by the formation of a covalent bond between the carbonyl carbon of the... 

Leucine aminopeptidase is interesting in that its active site contains two zinc atoms which together bind and activate the water molecule [74]. Despite this enzyme containing a dinuclear metal center at its active site, its mechanism, and specifically its mode of proton transfers reactions, appear to follow the general theme established by thermolysin and carboxypeptidase Adenosine deaminase and other members of the family of nucleoside and nucleotide deaminases utilize zinc-bound water as the catalytic nucleophile to displace ammonia from the 6-position of purines or the 4-position of pyrimidines and in all cases display inverse solvent deuterium isotope effects ranging from 0.3 to 0.8 on fec/Kni [75-80]. These effects are reminiscent of those observed for metallopro-teases and have their origins, like those of the proteases, in fractionation factors for the protons of the bound water that are less than one. 

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