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Structure and Substrate Specificity in the Serine Enzymes
Author(s) -
Blow D. M.
Publication year - 1974
Publication title -
israel journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.908
H-Index - 54
eISSN - 1869-5868
pISSN - 0021-2148
DOI - 10.1002/ijch.197400038
Subject(s) - chemistry , subtilisin , chymotrypsin , trypsin , tyrosine , residue (chemistry) , enzyme , serine , binding site , pancreatic elastase , stereochemistry , elastase , hydrolysis , biochemistry
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 S 1 is sufficient to ensure almost perfect orientation of the substrate for hydrolysis. For these enzymes further binding at S 2 and S 3 increases the binding energy slightly but has little effect on k cat . For subtilisin and elastase, binding at S 2 –S 4 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 S 1 can have a further significant effect on k cat . 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.