Chymosin molecules in the crystal lattice have Tyr77 occluding the S1/S3 substrate binding pockets suggesting that the enzyme is self-inhibited. An analysis of this structure in conjunction with its comparison with pepsin has shown that this is most probably an intrinsic property of the enzyme. It also indicates that chymosin's substrate specificity may be dependent upon the ability of the substrate to displace the tyrosine ring from the binding pockets. This analysis also implies that active and self-inhibited forms of other aspartic proteinases can exist in solution helping to explain the results of kinetic studies of these enzymes.
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