ON THE SPECIFICITY OF CARBOXYPEPTIDASE-N, A COMPARATIVE-STUDY

The structure of the enzymatically active subunit of human plasma carb oxypeptidase N was modeled based on the homology with bovine carboxype ptidase A. The active site of carboxypeptidase N is well conserved in comparison with carboxypeptidase A. From a comparison of energetically favorable binding sites for different atomic probe groups a hypothesi s for the differences in substrate specificity between carboxypeptidas es A and N was derived. Small synthetic peptide substrates were synthe sized to confirm this hypothesis. This study shows that even with very low homology model building by homology can be employed to build mode ls of sufficient quality to aid in drug design.