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C. Specificity<br />

Figure 4<br />

The inhibitors complexed with human (top) and mouse (bottom) renin<br />

showing the putative hydrogen-bond interactions made with the enzyme moieties.<br />

Page 333<br />

If the main-chain hydrogen bonding of substrates is conserved among aspartic proteinases, how are the<br />

differences in specificities achieved? Table 1 defines the enzyme residues that line the specificity<br />

pockets for both mouse and human renin. In modeling exercises (e.g., Reference 4) it was assumed that<br />

specificities derive from differences in the sizes of the residues in the specificity pockets (S n) and their<br />

ability to complement the corresponding side chains at positions P n in the substrate/inhibitor. A detailed<br />

analysis now shows that this simple assumption only partly accounts for the steric basis of specificity.<br />

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