Structure and Substrate Specificity in the Serine Enzymes

Publisher Website
Google Scholar
Abstract
Available data on the primary and secondary specificities of chymotrypsin, trypsin, elastase and subtilisin are reviewed in relation to their structures. For chymotrypsin and trypsin, proper binding in the main specificity pocket S1 is sufficient to ensure almost perfect orientation of the substrate for hydrolysis. For these enzymes further binding at S2 and S3 increases the binding energy slightly but has little effect on kcat. For subtilisin and elastase, binding at S2–S4 is important to maintain the correct orientation of the hydrolyzed bond. The mechanism proposed for subtilisin, whereby movements of 1 Å at P′1 stabilize the transition state of the reaction, seems unlikely to occur in chymotrypsin. For all these enzymes, proper orientation of the leaving group at S1 can have a further significant effect on kcat. Slight differences between the secondary specificities of trypsin and chymotrypsin are likely, owing to the presence of tyrosine at residue 151 and the deletion of residue 218 in trypsin.